
Glass. 
Book. 



COPYRIGHT DEPOSIT 



I 



HEMATOLOGICAL ATLAS 



DESCRIPTION OF THE TECHNIC 



BLOOD EXAMINATION 



BY 

Priv. Doz. Dr. Karl Schleip 

Scientific Assistant in the Medical Clinic University of Freiburg i/B. 



ENGLISH ADAPTATION OF TEXT 



BY 

Frederic E. Sondern, M.D. 

Professor of Clinical Pathology New York Post Graduate Medical School and Hospital, 
Director of Clinical Laboratory New York Lying-in Hospital. 



Wiitf) 71 Colore* Murtrationg 




NEW YORK 

REBMAN COMPANY 

1123 BROADWAY 



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LIBRARY of CONFESS.! 
Two Copies Kettivc 

FEB 4 1^08 

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Copyright, 1908, by 
REBMAN COMPANY 

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Entered at Stationers' Hall, London, Eng., 1908 



All rights reserved 



Printed in America 



©ebtcateb to 

GEHEIMRAT PROFESSOR DR. CHR. BAUMLER 



PREFACE TO THE ENGLISH EDITION 

The paucity of good pictures illustrating the changes 
in the microscopic appearance of the blood which 
have become apparent by the use of panoptic staining 
methods is evident to the teacher of Clinical Hema- 
tology. To this fact noted by the author, and to the 
opportunities offered him by the hematological ma- 
terial available at the Medical Clinic of the University 
of Freiburg, this Atlas owes its origin. An accurate 
picture of characteristic changes is often better than a 
detailed description or an imperfect specimen. 

The object of the Atlas is not only to assist in teach- 
ing the subject but also to serve as a guide for the 
private study of the clinician; and the brief diagnostic 
points and explanatory comments may be of value in 
this connection. In the nomenclature of the blood 
cells the universally used terms have been selected, 
and those based on theories not yet firmly established 
have been avoided. 

A sufficiently detailed technic of the clinical 
methods used in blood examination has been in- 
cluded with the hope of enhancing the usefulness of 
the book, and the complicated procedures demanding 
extensive apparatus and not suited to the use of the 
clinical worker have been omitted. The original 
illustrations represent specimens stained with the 
Leishman modification of the Romanowsky method, 
and uniform magnifications of 330 and 750 only have 
been used. 



Few slight changes have been made in the English 
adaptation of the text where these seemed indicated 
by different customs and racial characteristics, but 
classifications, nomenclature, etc., are strict transla- 
tions of the original. 

Frederic E. Sondern. 

New York City. 



VI 



TABLE OF CONTENTS 

PAGE 

Examination of the Blood by Clinical Methods 1-12 
Obtaining the Blood and Preparation of Dried Films 3 
Estimation of the Amount of Hemoglobin . . 4 

Counting the Blood Corpuscles .... 5 
Differential Count of Leucocytes .... 9 
Examination of the Fresh Blood . .10 

Staining the Dried Films . . . . .11 

Estimation of the Specific Gravity . . . .12 



Development of White and Red Blood Corpuscles 15-21 
Plate I 



Normal Blood . 
Plates II-III 



23-31 



The White Corpuscles of the Human Blood 
Plates IV- VII 



33-55 



The Varieties of Leucocytosis 
Plates VIII-XIII 
Neutrophilic Leucocytosis 
Eosinophilic Leucocytosis 
Leucocytosis in Children 
Lymphocytosis 



57-85 

. 59 

. 67 

. 75 

. 81 



The Red Corpuscles of the Human Blood and Blood 

Platelets 87-93 

Plate XIV 



The Anemias 

Plates XV-XXII 
Polychromatophilia 
Basophilic Granulation 



95-137 

. 97 
. 103 



vn 



PAGE 

Secondary Anemias 109-123 



Primaey Anemias 125-137 

Chlorosis 131 

Pernicious Anemia . . . . . .135 

Leukemias ....... 139-215 

Plates XXIII-XXXVII 

Chronic Lymphatic Leukemia .... 153 

Myelogenous Leukemia . . . . .173 

Acute Leukemia ....... 207 

Blood Changes Associated with Tumors of the Bone 

Marrow 217-231 

Plates XXXVIII-XL 

Carcinoma of the Bone Marrow . . . .219 

Sarcoma of the Bone Marrow .... 225 

Leukosarcomatosis ...... 229 

Blood Parasites 233-257 

Plates XLI-XLV 

Tertian Malaria 239 

Quartan Malaria ....... 249 

Estivo-autumnal Malaria ..... 249 

Trypanosomiasis ....... 253 



vm 






TECHNIC OF CLINICAL METHODS 

FOR 

EXAMINATION OF THE BLOOD 



Obtaining the Blood and Preparing the 
Dried Films 

The blood is usually obtained from the lobe of the 
ear or the tip of the finger by a rapid puncture with 
one of the various blood lancets or a straight Hage- 
dorn needle of medium size. Experience develops 
good technic and if the procedure is rapid there is 
practically no pain or subsequent discomfort. Previ- 
ous cleansing of the skin is desirable, for by thus 
softening it the puncture is more easily made. The 
blood should flow slowly of its own accord and with- 
out pressure on the immediately surrounding tissues. 
The first drop of blood and any moisture of the skin 
should be wiped away and the following small drop 
taken up on the surface of a cover-glass very close to 
its edge. A slide, which has been carefully cleaned, 
is held by the left-hand end and the edge of the cover- 
glass placed in contact with it at the other end, and 
inclined to the right until the blood drop also touches 
the slide and spreads the entire width of the cover- 
glass. 

Held in this position the cover is now rapidly 
pushed over the surface of the slide toward the left 
hand, the drop being drawn along behind it. Any 
injury to or distortion of the corpuscles is avoided by 
this method, as no pressure is used, and while the 
resulting spread is rather thick where begun, it is 
quite thin and uniform toward the middle and left 
end of the specimen. 

Several precautions should be observed. The 
cover-glass should not come into contact with the 
skin while it is being charged with blood, and the 
smaller the amount used, the better the resulting film. 

3 



The cover-glass used for spreading must have an 
absolutely smooth edge, otherwise the leucocytes 
may be distributed unevenly, thus jeopardizing the 
accuracy of the differential count. The whole pro- 
cedure should be accomplished as quickly as possible 
so that comparatively little time elapses between the 
appearance of the drop of blood and the drying of 
the prepared films. 

Estimation of the Amount of Hemoglobin 

In the application of clinical methods in blood 
examination, several procedures and appliances for 
determining the amount of hemoglobin must be con- 
sidered. There are numerous good methods, but 
none as yet without some disadvantage. In most 
of the clinical methods employed, the diluted blood is 
compared with some artificially colored substance. 
In the Fleischl-Miescher hemometer this substance 
consists of a wedge-shaped piece of stained glass 
while in the Gower's hemoglobinometer a glycerin 
jelly stained with picro-carmin is used. Both of 
these methods are trustworthy and universally used, 
but the new Sahli hemometer deserves special 
mention. 

The Sahli Hemometer 

The inference is reasonable that the best colori- 
metric determination can be made by comparing the 
solution to be tested with one of known strength con- 
taining the identical pigment. While a solution of 
hemoglobin would be the ideal standard, this is not 
feasible on account of its rapid deterioration. Con- 
sequently, Sahli employs a stable hemoglobin deriv- 
ative as a standard, and converts the blood to be 
examined into the same derivative before the deter- 
mination is made. The principle is as follows : One 
part of blood is mixed with ten parts of decinormal 
hydrochloric acid in a graduated tube, with the result 
that an acid hematin is obtained, quite constant in 

4 



color and composition. This dark brown fluid 
dilutes to a clear yellow with water and is well 
adapted to colorimetric estimation. The standard 
solution is sealed in a comparison tube of exactly the 
same caliber and corresponds to a 1 per cent, solution 
of normal blood. 

To apply the test, the graduated tube is filled with 
decinormal hydrochloric acid to the 10 per cent, 
point, to which 20 c.mm. of blood obtained with the 
capillary pipette is added, and the whole carefully 
shaken. As soon as the mixture assumes a clear 
dark brown color, water is added drop by drop until 
the tint corresponds to that of the standard tube. 
The percentage of hemoglobin is read from the point 
of the scale corresponding to the height of the solution. 

Counting the Blood Corpuscles 

It is very essential that the blood used for this pur- 
pose be taken as quickly after the puncture as possible 
with accurate technic, in order to avoid sources 
of considerable error. The Thoma-Zeiss counting 
chamber can be recommended for the separate 
estimation of red cells and leucocytes, but for greater 
convenience and accuracy in the leucocyte count or 
when leucocytes and red cells are to be counted in 
the same preparation, the chambers ruled according 
to Zappert or Tiirk are preferable. 

Diluting Fluids 

In order to count the red corpuscles it is necessary 
to dilute the blood with a fluid which will prevent 
coagulation and cause no change in the cellular ele- 
ments. One of the following may be used: 

Hay em's Solution: 

Gram 

Bichloride of Mercury 0.5 

Sulphate of Sodium 5.0 

Chloride of Sodium 1.0 

Distilled Water 200.0 

5 



Toissorts Solution: 

Gram 

Methyl Violet 5 B 0.025 

Chloride of Sodium 1.0 

Sulphate of Sodium 8.0 

Glycerin 30.0 

Distilled Water 160.0 

For the purpose of counting the leucocytes a dilut- 
ing fluid is required which lakes the red corpuscles 
and not only preserves the white cells but also makes 
their nuclei more distinct. This is accomplished by 
the use of 0.3 to 0.6 per cent, solution of glacial acetic 
acid to which a few drops of concentrated aqueous 
solution of gentian violet may be added to stain the 
nuclei. 

Counting the Red Corpuscles 

The Thoma-Zeiss hemocytometer consists of the 
following: 

1. The Mixing Pipette is a graduated thick-walled 
capillary tube pointed at one end and dilated into a 
bulb at the other, with a short tube at the opposite 
pole of the bulb to which the rubber aspirating tube 
is attached. The bulb contains a small glass ball to 
facilitate the mixing. The capillary tube bears the 
graduations 0.5 and 1.0 and the upper end of the 
bulb is marked 101, indicating that the capacity of 
the bulb is 100 times that of the capillary tube. 

2. The Counting Chamber consists of a heavy glass 
slide on which a square glass plate, with a circular 
opening 1 cm. in diameter, is cemented. A circular 
glass disk 8 mm. in diameter is cemented in the center 
of this opening in such a way that a ditch separates 
the two, the slide forming its floor. The surface of 
the central disk is exactly 0.1 mm. lower than the 
level of the outer glass plate and forms the floor of the 
counting chamber. Its center is ruled in such a way 
that 400 small squares are formed each having an 
area of ^^ sq. mm. An extra line is ruled through 
each fifth row of squares, as shown in the accompany- 

6 



ing illustration, to facilitate the counting. The upper 
limit of the chamber is formed by a superimposed 
absolutely plane cover- 
glass. 

The red cell count is 
made as follows : ! 

After the puncture, 
made in the usual way, 
a rather large drop of 
blood is allowed to col- " 
lect, and this is -rapidly I 
drawn into the pipette " 
to the mark 1.0. After " 
wiping the point, it is 
plunged into a bottle containing the diluting fluid. 
While this is being drawn into the bulb the pipette 
should be twirled between the fingers to mix the 
blood and diluting fluid. When the mark 101 is 
reached, aspiration is stopped, the rubber tube re- 
moved, and with the thumb on the point and the 
middle finger closing the other end, the whole gently 
shaken. Some experience is necessary before perfect 
technic is acquired. As the fluid remaining in the 
capillary tube does not enter into the mixture, the 
bulb now contains 1 part blood and 99 parts diluting 
fluid. If the blood has been drawn to the mark 0.5 
the dilution is 1 in 200, instead of 1 in 100 as above. 

The rubber tube is again attached, a few drops 
blown out, the point wiped dry, and the next small 
drop placed in the center of the scrupulously clean 
counting chamber, over which the polished cover- 
glass is placed with some pressure. If the contact is 
perfect, as it must be if accurate results are desired, 
the Newton's rings are visible. The drop used must 
not be too large or some of it will fill the ditch and 
run between the cover and the outer glass disk. In 
this case it is necessary to repeat the procedure with a 
smaller drop. 

The slide is now left undisturbed for about five 

7 



minutes to allow the corpuscles to settle on the bottom 
of the chamber. The counting of the corpuscles is 
best done with a magnification of about 300, which 
presents a good picture of the network of squares. 
The area of each small square is 7 ^ sq. mm., and the 
distance between the floor and the lower surface of 
the cover is T V mm., consequently each square repre- 
sents jto cu. mm. The cells in a large number of 
these squares are now counted, including those which 
touch or overlap the upper and left-hand boundary 
lines, but not those which touch or overlap the lower 
and right-hand boundary lines. With proper technic 
the corpuscles are uniformly distributed and counting 
those in 100 small squares is usually sufficient. If a 
dilution of 1: 100 has been used, the calculation will 
be as follows: Supposing 1,450 corpuscles were 
counted in 100 small squares, each square will average 
"nnr corpuscles. As each square represents a height 
of T V mm. and a surface of 4^ sq. mm., each cubic 
mm. contains 10 X 400 = 4,000 times as many cells. 
A dilution of 1 : 100 having been used the blood con- 
tains 100 times as many cells as the dilution. There- 
fore the formula for the calculation will be, 

1,450 x 4,000 x 100 

~jd = 1,450 X 4,000 = 5,800,000 

red corpuscles in 1 cu. mm. of blood. 

The careful cleaning of the pipette is important, 
and this is accomplished by putting the rubber tube 
on the capillary tube end of the pipette and drawing 
water through it. This is followed by alcohol and 
then by ether, the latter being allowed to run out first 
one end and then the other by itself. Air is then 
sucked through by mouth or aspirator until the in- 
terior is dry. The counting chamber is rinsed in 
water only. 

Counting the Leucocytes 

For the enumeration of the leucocytes, large bore 
pipettes are usually employed, with a resulting dilu- 



tion of 1 :10 or 1 :20, the bulb holding but 10 times as 
much as the capillary tube. After the dilution with 
the acetic acid solution has been made, the procedure 
is the same as in counting red corpuscles. 

For reasons mentioned, a chamber with Zappert 
ruling should preferably be used for leucocytes, as it 
admits of counting 2,000 small squares in one speci- 
men. Supposing the dilution was 1:10, and 2,000 
squares were counted, the calculation would be 

X x 4,000 x 10 X x20 
2,000 

Extreme care and accuracy are absolutely essential 
in every blood cell count, if the result is to be correct. 
Beginners cannot possibly avoid all sources of error, 
and practice is undoubtedly necessary before a proper 
and uniform technic can be acquired. 

The Differential Count of Leucocytes 

Owing to the development in the knowledge of 
blood changes in disease, a proper estimation of the 
condition of the blood usually demands information 
concerning the relative percentage, or the absolute 
number, of the different varieties of leucocytes pres- 
ent, in addition to the total leucocyte count. Fluc- 
tuations in the quantitative relation of the various 
forms are not uncommon and may present a differ- 
ential count suggestive or pathognomonic of a given 
disease. In other cases, valuable prognostic data 
may be derived from the differential count. 

Evenly spread and stained blood films are em- 
ployed for the count, and the use of a mechanical 
stage is desirable. The easiest method of tally is to 
have another person note the cells as called, but in 
the absence of such help the number of neutrophiles 
may be kept in mind and the other varieties noted on 
paper. With a little practice every one usually 
devises a convenient scheme. A minimum of 300, 
but preferably 500, cells should be counted in order to 

9 



secure approximately reliable results. The relative 
or percentage value of each variety is then figured, 
and the absolute count should also be determined, 
by applying the percentages to the total leucocyte 
count made by means of the counting chamber. 

While making the differential count, the character 
of the red blood cells, the approximate number of 
blood platelets, and the presence or absence of 
nucleated red cells or plasmodia of malaria should 
also be noted. 

Examination of Fresh Blood 

The examination of fresh blood in its moist un- 
stained state is frequently conducted in an improper 
manner. When a drop of blood is examined between 
slide and cover-glass, evaporation and mechanical 
injury are apt to occur, and the degree of poikilocy- 
tosis, for example, cannot be properly estimated. 
Under these conditions the use of an oil-immersion 
objective is also difficult, as the cover-glass may float 
on the layer of blood. 

The following procedure is recommended: A ring 
of cedar oil is applied around the edge of the concave 
depression in a hanging drop slide. A perfectly clean 
square cover-glass is prepared and a likewise clean 
small piece of cover-glass about 4 mm. in diameter is 
placed on the center of it. The large bore Thoma- 
Zeiss pipette is then filled with fresh blood and 
diluted in proportion of 1:10 with physiological salt 
solution. After mixing and blowing out a few drops, 
a little of the diluted blood is allowed to run between 
the two cover-glasses, as prepared, and the inverted 
concave slide placed in such a position that the oil 
ring is in perfect contact with the larger cover-glass. 
The specimen is then turned right side up and has 
the appearance as illustrated. 

The completed specimen of diluted blood is thus 
prepared in a way which certainly prevents evapora- 
tion and mechanical injury. The capillary layer is 

10 



preferable to the hanging drop, and the dilution is 
employed, as it permits a more careful study of the 
shape of individual corpuscles than is possible when 
undiluted blood is examined. The specimens may 
be examined with a low or high power, and if kept 



d.c. 

a. Slide with concave center. 

b. Large cover-glass. 

c. Chamber made air tight by the layer of oil between a. and b. 

d. Small piece of cover-glass, held to the under surface of b. by the interven- 

ing capillary layer of blood. 

warm will show all the characteristics even after the 
lapse of hours. The excellent results obtained by 
means of this method are well shown in Table II, 
Figure 3. Staining fluids may be added to the dilut- 
ing solution for the easier recognition of leucocytes, 
five drops of an aqueous solution of gentian violet 
to each 10 c.c. of salt solution being recommended. 

Staining the Dried Films 

The Romanowshy method, or one of its numerous 
modifications, is in almost universal use at present 
for staining dried blood spreads. For some years 
the author has used the Leishman* modification 
almost exclusively. This is an eosinate of methylene 
blue dissolved in methyl alcohol, which fixes and 
stains the specimens simultaneously. The Leishman 
is a panoptic stain, and preferable on account of the 
simplicity of the procedure. It is used as follows: 
The air-dried blood film, without previous fixation, 
is covered with about ten drops of staining fluid. 
After about thirty seconds, double this amount of 

* W. B. Leishman. A Simple and Rapid Method of producing Roman- 
musky Staining in Malaria and other Blood Films. British Med. Journ., 
Sept. 21, 1901. 

11 



distilled water is added to and mixed with the stain. 
Five minutes later the mixture is washed oft' with 
water, and the slide dried between lintless blotters. 
If the specimen is overstained, the erythrocytes have 
a deep red or greenish tint. This can be remedied 
by allowing a few drops of distilled water to remain 
on the slide for one or two minutes, after which it is 
washed and dried as before. The entire procedure 
of spreading the blood, drying, staining and placing 
the specimen under the microscope should not con- 
sume more than seven or eight minutes. Only one 
reagent and a little distilled water are needed for the 
staining. The results of the method are shown on 
the following pages, and particular attention is called 
to Plates IV, V and XV. 

The stained specimen can now be studied with a 
low power or with an immersion lens, a permanent 
mounting in balsam being unnecessary. If balsam 
is used, it is well to remember that an acid balsam 
decolorizes the specimen after a time. The cedar oil 
used on unmounted specimens can be removed with 
xylol without injury to the blood film. 

Estimation of the Specific Gravity 

A knowledge of the concentration of the blood is of 
considerable importance in a number of diseases. 
The experienced observer will immediately note 
decided changes in this respect by the appearance of 
the blood, which observation is sufficiently accurate 
to determine the degree of dilution best suited to the 
general blood examination about to be made. 

The Schmalz method of determining the specific 
gravity by means of a capillary pycnometer is useful 
and accurate, but requires experience. A glass tube 
about 10 cm. long, constricted at both ends and hold- 
ing 0.2 c.c. of fluid, is weighed empty on an accurate 
balance sensitive to 0.1 mg. It is then filled with 
distilled water and again weighed. The difference 

12 



represents the weight of the water held by the tube. 
After thorough drying the tube is filled with blood 
and the outer surface carefully cleaned. The net 
weight of the blood divided by the weight of the water 
will indicate the specific gravity of the former. The 
normal specific gravity of the blood is variously 
stated, but averages 1052 to 1058 in men and 1048 
to 1055 in women. 






13 



DEVELOPMENT 

OF 

WHITE AND RED BLOOD CORPUSCLES 

PLATE I FIGURE 1 



PLATE I 

Figure 1.— The Development of White and 
Red Blood Corpuscles 

The normal and pathological cells of the human 
blood all probably originate in the bone marrow, 
with the exception of the lymphocytes. Of these a 
small number are derived from the bone marrow, but 
by far the larger number come from the lymph 
glands. 

A previous study of the manner of development of 
the different cells according to the generally accepted 
theory, will lead to a better understanding of the 
clinically important changes in the blood, the signifi- 
cance of individual cells and the relations they bear 
to one another. 

All human blood cells can easily be traced to one 
parent form (1). An unbroken series of cells repre- 
senting successive stages of development are found 
between this parent form and the normal cells of the 
blood. The cells closest to the parent form show 
different characteristics at an early period by assum- 
ing either a basophilic (2) or a neutrophilic (3) proto- 
plasm. Subsequently, these cells develop into other 
forms (4 and 5), constituting, on the one hand, a 
transition into the mature neutrophilic granular cells 
of the bone marrow (6), the so-called neutrophilic 
myelocytes, and, on the other hand, pass, by further 
intermediate stages, into lymphocytes (13) and transi- 
tional forms (15). The term "transitional form" is 
derived from the older interpretation of this cell as a 
preliminary stage of the polymorphonuclear neu- 
trophile, or as an intermediate stage between that cell 
and the neutrophilic myelocyte. This view is scarcely 

17 



:a'Mi 



justified at the present state of our knowledge and it 
is probable that the transitional form also represents 
a terminal cellular type incapable of further develop- 
ment. 

The large cell with homogeneous basophilic proto- 
plasm (2) also gives rise, by way of intermediate 
stages, to the basophilic myelocyte (8), which in turn 
is transformed into the basophile (11). The eosino- 
phil (12) may be derived, by way of the eosinophilic 
myelocyte (9), from the preliminary stages of the 
basophilic myelocyte. A close relationship probably 
exists between the basophilic and the eosinophilic 
myelocyte, notwithstanding their dissimilar staining 
qualities, as intermediate stages between these two 
cells are not infrequently encountered in leukemic 
blood. Basophiles are invariably found increased in 
cases of relative eosinophilia, and the association of 
these mature cells is a common clinical phenomenon. 

The neutrophilic leucocyte (10) is derived from the 
neutrophilic myelocyte (6) in the same way as the 
normal eosinophile and basophile (12 and 11) develop 
from the corresponding eosinophilic myelocyte (9) 
and the basophilic myelocyte (8) . The rare irritation 
form of Turk (14) is at present interpreted as a 
lymphocyte, the further development of which is due 
to a pathological stimulus, and not as a preliminary 
stage of the mature lymphocyte (13), as formerly 
believed. 

The erythrocytes can also be traced, by direct 
transition, to the parent cell; the large mononuclear 
cell with homogeneous basophilic protoplasm (2) 
being a forerunner of the megaloblast (16). The 
megaloblast in its early stage may have a voluminous 
basophilic cell body and a relatively large nucleus 
and, occurring in the peripheral circulation, is often 
distinguished with difficulty from the Turk irritation 
form (see Fig: 41). As the result of the further 
development of the megaloblast, the normoblast is 
formed, and subsequently the erythrocyte (17). 

18 



Plate I represents a genealogical scheme of develop- 
ment, including the chief types only. In the designa- 
tion of cells the suggestion of Grawiiz is recommended, 




that for the present the terms having definite signifi- 
cance, such as "myelocyte," be adhered to, with the 
additional characteristic attached, for example : neu- 

19 



trophilic myelocyte, eosinophilic myelocyte, etc., 
rather than the arbitrary nomenclature suggested by 
different authors. 

In the development of all blood corpuscles, the 
following chief forms must be considered : 

1 . Large mononuclear cell with pale homogeneous 
cell body = parent cell. 

2. Large mononuclear basophilic cell. 

3. Large mononuclear neutrophilic cell. 

4. Mononuclear basophilic cell in which there are 
few neutrophilic granules. 

5. Mononuclear neutrophilic cell in which there 
are few neutrophilic granules. 

6. Mononuclear cell with dense neutrophilic gran- 
ulation = neutrophilic myelocyte. 

7. Mononuclear basophilic cell with beginning 
basophilic granulation. 

8. Mononuclear cell with basophilic granulation 
= basophilic myelocyte. 

9. Mononuclear cell with eosinophilic granula- 
tion = eosinophilic myelocyte. 

10. Neutrophile. 

11. Basophile. 

12. Eosinophile. 

13. Lymphocyte. 

14. Turk irritation form. 

15. Transitional form. 

16. Erythroblast. 

17. Erythrocyte. 






20 



Plate I. Fig. 1 




S A 



74 






NORMAL BLOOD 

PLATES II AND III FIGURES 2-5 






PLATE II 

Figures 2 and 3.— Normal Blood 

The blood of healthy individuals presents certain 
physiological variations within comparatively narrow 
limits. The average composition is approximately 
as follows: 

Children \ to 15 years: Hemoglobin, 70 to 80 per cent.; red cells, 
4,900,000; leucocytes, 9,000 in 1 c. mm. 

Men: Hemoglobin, 90 to 100 per cent.; red cells, 5,100,000; leuco- 
cytes, 7,500 in 1 c. mm. 

Women: Hemoglobin, 85 to 95 per cent.; red cells, 4,500,000 to 
5,000,000; leucocytes, 7,500 in 1 c. mm. 

Healthy Man, 32 years old: Hemoglobin, 120 per cent.; red cells, 
5,600,000; leucocytes, 7,800. 

Figure 2.— Fresh Double Cover-Glass Speci- 
men Unstained. Magnification 330 

The pale yellow color of the erythrocytes is the 
characteristic normal hemoglobin tint. The cells 
are uniform in size, some appearing cup shaped on 
account of their position. The detailed structure is 
more apparent when a higher power is used. 

Figure 3.— The Same Specimen. Magnifi- 
cation 750 

Normal red blood corpuscles appear cup shaped 
with thickened walls. This appearance is only 
noted as long as injurious influences are excluded, 
such as evaporation, drying from any cause, hyper- 
tonia, isotonia, cold or heat, which cannot always be 
prevented, even by experienced workers. This cup 

24 



shape is best noted in the corpuscles lying by them- 
selves ; the convexity is apparent, and on the opposite 
side the concavity of the cup can be seen, its rounded 
margin merging into the outer wall of the Blood cell. 

The lateral aspect of the red corpuscle is well 
curved and sausage shaped, on the concave side of 
which there is a light transparent wall with convex 
margin. If the corpuscle lies so that the open end 
of the cup can be looked into, the appearance is that 
of a circle with a sharply defined, lighter colored 
center. This light center corresponds to the trans- 
parent crest at the floor of the cup, and the darker 
colored outer ring to the relatively much thicker wall 
of the cup. 

Seen from above the corpuscle appears globular, 
and the cup-shaped form can only be noted on 
focusing a lower level. Most of the red corpuscles 
in the double cover-glass specimen present this 
appearance. 

Deviations from this fundamental form are noted, 
but these have as yet assumed no pathological sig- 
nificance. The cup shape may be more or less pro- 
nounced and the opening may vary in width. 

The erythrocyte is frequently seen in the form of a 
biconcave disk, both concavities occupied by a con- 
vex transparent membrane. This appearance is 
explained by the crest of the bell having become in- 
dented by contact with another corpuscle. These 
indentations are rarely seen in the lateral wall of the 
corpuscle. When the red corpuscles are close to- 
gether the so-called rouleaux formation occurs as the 
result of crowding, the concave portion of one cor- 
puscle slipping over the convex portion of the adja- 
cent one. In this condition the actual form of the 
corpuscles cannot be made out. (See Figs. 16, 35, 
37, 38, 42, 43, 46 and 51.) (Weidenreich.) 

Three leucocytes are also seen in the field; the 
smallest, with a round nucleus surrounded by a nar- 
row rim of protoplasm, is a lymphocyte. The larger 

25 



cell on the left with polymorphonuclear configuration 
and dense finely granular protoplasm is a poly- 
morphonuclear leucocyte. The cell above presents 
a striking appearance, the nucleus consisting of 
several portions connected by thin nuclear strands. 
The protoplasm is filled with coarse, round, strongly 
refractive granules, some lying apparently beyond 
the cell but actually within protoplasmic processes of 
the cell, which is in slight ameboid motion. This 
cell is an eosinophile which is identified in the fresh 
specimen by its highly refractive coarse granulation. 



36 



Plate II. Figs. 2, 3 





PLATE III 
Figures 4 and 5. — Normal Blood 






i 

i 



The same case. 

Figure 4.— Stained Specimen. Magnifica- 
tion 330 

All the erythrocytes are uniform in size and, on 
account of being spread, are seen as flat circular 
yellowish-red disks, the cup shape not being apparent. 
While some seem uniformly pigmented, the majority 
have a lighter colored central zone and a darker 
periphery, which is due to the original cup shape of 
the corpuscle. The details are more apparent with 
the use of a higher power. 

The same case. 

Figure 5. — Stained Specimen. Magnifica- 
tion 750 

The appearance of the erythrocytes is more dis- 
tinct in this specimen. The depressed center, being 
a thin wall, is faintly stained, while the thicker edge 
has a deeper tone. A neutrophilic leucocyte and 
two lymphocytes of different size are also seen in the 
field. 



Plate III. Figs. 4, 5 











THE WHITE CORPUSCLES 

OF 

THE HUMAN BLOOD 

PLATES IV-VII FIGURES 6-15 



PLATES IV- VII 

Figures 6- 15.— Leucocytes of the Human 

Blood 

Not Including Cells of the Bone-Marrow 

The number of leucocytes in 1 c. mm. of blood in 
an adult is approximately 7,500. These consist of a 
variety of different forms, which, under normal cir- 
cumstances, are present in a definite numerical ratio 
to one another. This enumeration is known as the 
"Differential Count of Leucocytes," and the follow- 
ing are the normal varieties and figures: 

Polymorphonuclear Neu- 

trophiles 65 to 70 per cent, or 4,900 to 5,300 in 1 c.mm. 

Lymphocytes 20 to 25 per cent, or 1,500 to 2,000 in 1 c.mm. 

Transitional Forms 3 to 5 per cent, or 230 to 380 in 1 c.mm. 

Eosinophiles . 2 to 4 per cent, or 150 to 300 in 1 c.mm. 

Basophiles \ per cent, or 40 in 1 c.mm. 

Turk's Irritation Forms rarely occur. 

In children under 5 years of age, the lymphocyte is 
the predominating cell, and the polymorphonuclear 
neutrophiles usually amount to less than 50 per cent. 









35 



III 



w 



PLATE IV 

Figure 6. — Neutrophilic Leucocytes 
Figure 7. — Lymphocytes 
Figure 8. — Transitional Forms 



i 



Figure 6. — Polymorphonuclear Neutro- 
phils. Magnification 750 

These cells are usually about twice the size of an 
erythrocyte, rarely larger. The nucleus is character- 
ized by its polymorphous configuration, some of the 
portions often being connected by thin nuclear 
strands. Apparently separate nuclear segments are 
occasionally seen, but these have "underground" 
connection, as the cells are never polynuclear. The 
protoplasm is neutrophilic and shows close fine 
granulations which are especially apparent in cases 
of leucocytosis, but are occasionally so slight that 
they cannot be brought out even in overstained 
specimens. The neutrophilic quality of the proto- 
plasm also varies, and these differences are probably 
due to different ages and functions of the cells, 
rather than to any fault in staining. 

Figure 7.— Lymphocytes. Magnification 

750 

The cells are extremely varied in size and some 
show a narrow, others a broad ring of protoplasm. 
The majority are small, little larger than an ery- 
throcyte, but very large forms, four or five times the 
size of the small ones are frequently seen in children, 
and occasionally in adults. The nucleus is usually 
round and sometimes indented, and in the larger 
forms it is oval or polygonal. It stains deeply in the 
small cells and rather faintly in the larger ones and 
two or more nucleoli may become visible. The 
protoplasm is slightly basophilic, — more so in the 
small cells than in the large ones, — and occasionally 

39 



the outer zone stains darker than that close to the 
nucleus. The large lymphocytes may present angu- 
lar or irregular outlines. A smaller or larger number 
of all lymphocytes show acidophilic granulation, 
which appears as fine particles or angular granules. 
This is noted in every specimen and has no patho- 
logical significance as yet. 

Figure 8.— Transitional Forms. Magnifica- 
tion 750 

These cells are invariably larger than the poly- 
morphonuclear neutrophiles and frequently irregu- 
larly round in outline. (The irregular outline as in 
the case of the large lymphocytes is probably referable 
to adjacent erythrocytes, or those in close proximity.) 
Compared with the other lymphocytes, the nucleus 
is always paler and poorer in chromatin. It is 
usually horseshoe shaped or multilobular, rarely 
round and indented. The protoplasm is slightly 
basophilic and contains more or less marked neu- 
trophilic granulation most apparent in the nuclear 
indentations. With these characteristics in mind, 
the cells are easily differentiated from the polymor- 
phonuclear neutrophiles. 



40 



Plate IV. Figs. 6, 7, 8 



*s *> m a 




.'J;;jflBiiB>''.! 







••^i% 






^iiP< 



-1 



o * 












• # t 






ft c * 
* # A 













PLATE V 



Figure 9.— Eosinophils 
Figure 10.— Basophiles 
Figure 11.— Turk's Irritation Forms 






Figure 9.— Eosinophiles. Magnification 

750 

These are very striking and easily identified round 
cells of the same size as polymorphonuclear neu- 
trophiles, rarely larger or smaller. They frequently 
have two or three oblong or oval nuclear portions 
connected by thin nuclear strands, which are occa- 
sionally unequal in size. 

The protoplasm is faintly basophilic and shows a 
bright-red coarse granulation. The granules are 
round, varying in number, and may be arranged in 
groups. Some cells are so densely filled with granules 
that they can scarcely be distinguished. 

In one case of trichinosis, the author found a cell 
containing an equal number of eosinophilic and 
basophilic granules (see Fig. 9) . 

Figure 10. — Basophiles. Magnification 

750 

These cells vary in appearance and are about the 
size of an eosinophile. They occur less frequently, 
and are not as easily recognized. The nucleus 
occupies about two-thirds of the cell, usually pre- 
senting the outline of a clover-leaf or rosette, rarely 
round or indented, with no defined margin. The 
protoplasm shows a fine basophilic or eosinophilic 
network. Round coarse granules of varied size are 
seen at the points of intersection, or these may fill 
the entire cell and lie on the nucleus. The granules 
take a deep chromatin stain and have basic properties. 
The cells are occasionally free from granules and 
then vacuoles are found in the network. 

45 



-= 



■V 



Figure 11. — Turk's Irritation Forms. 
Magnification 750 

These cells are only found in pathological blood 
after leucocytoses and inflammatory processes. They 
resemble the large lymphocytes in type, have a 
large nucleus poor in chromatin, and frequently 
small nucleoli. The nucleus is not always in the 
center of the cell and is surrounded by a band of 
protoplasm which varies in width and takes a dark 
blue stain. Vacuoles may be found in the cell body. 
Amitotic nuclear division figures are not uncommon. 



46 



Plate V. Figs. 9, 10, 11 









a&h 







_i 










11 





*• ' 





PLATE VI 

Figure 12. — Two Eosinophils and Two 
Transitionals 

Figure 13. — Two Transitionals and Two 
Basophiles 






Figures 12 to 14 show some of the above described 
leucocytes, as well as a comparison in appearance 
and size between one another, and the erythrocytes. 

Figure 12 Two Eosinophils and Two 

Transitionals. Magnification 750 

In the eosinophils, the characteristic configuration 
of the nucleus and the arrangement of the distinctly 
stained granules are particularly evident. The two 
transitionals present characteristics by means of 
which they are easily distinguished from polymor- 
phonuclear neutrophils (see Fig. 6). A few blood 
platelets are seen on the left. 



Figure 13 Two Transitionals and Two 

Basophiles. Magnification 750 

The upper transitional appears as a large mono- 
nuclear leucocyte. Close inspection shows an in- 
dented and constricted nucleus. The lower transi- 
tional has a lobular nucleus and is probably a more 
mature cell. 

Two basophiles are seen on the right with differ- 
ently shaped nuclei and coarsely granular protoplasm. 



50 



Plate VI. Figs. 12, 13 





i 



PLATE VII 

Figure 14. — Lymphocytes 

Figure 15. — Degeneration Forms of 
Leucocytes 






"»» 



Figure 14. — Lymphocytes. Magnification 

750 

The lymphocytes shown in the picture represent 
an infrequently observed type, and may occasion 
diagnostic difficulty. The two upper cells illustrate 
the maximum size of the usually much smaller lym- 
phocyte. The nuclei are poor in chromatin and 
show distinct nucleoli. The acidophilic granules are 
well brought out by the Romanowsky stain in all 
three of the cells. 

Figure 15.— Degeneration Forms of Leuco- 
cytes. Magnification 750 

Two neutrophiles are seen above, two lymphocytes 
to the left, a transitional below, a Turk's irritation 
form on the right and an eosinophile in the center. 

All these cells show vacuoles varying in size and 
number. These changes are usually noted in speci- 
mens from much debilitated or moribund patients 
many hours before death. One of the polymorpho- 
nuclear neutrophiles in the picture has been dis- 
tended, and finally ruptured by the increase in size 
of the vacuoles. 

In the transitional, the zonal stain and the marginal 
arrangement of the vacuoles are noteworthy, and 
probably due to lessened resistance at the periphery 
of the protoplasm. 

The occurrence of this vacuolar degeneration in a 
large number of leucocytes would thus seem to be a 
bad prognostic sign. 



54 







Plate VII. Figs. 14, 15 



I 





THE LEUCOCYTOSES 

PLATES VIII- XIII FIGURES 16-23 







PLATE VIII 
Figure 16.— Neutrophilic Leucocytosis 






mm 



Neutrophilic Leucocytosis. The diagnosis of this 
condition is based not only on an increase in the 
relative percentage of polymorphonuclear neutro- 
phils in the differential count but also on an absolute 
increase as well. The lowest figures which con- 
stitute a neutrophilic leucocytosis are approximately 
8,000 neutrophiles in 1 c.mm. the total leucocyte 
count being about 10,000. The maximum figures 
are indefinite, but counts over 60,000 neutrophiles in 
1 c. mm. are rare. This is the most common type 
of leucocytosis. The lymphocytes and eosinophiles 
are usually decreased both in relative percentage and 
in absolute numbers. 



Female, 16 years old. Pleurisy and Exudative Pericarditis. Leu- 
cocytes, 34,200 in 1 c.mm. 

Figure 16. — Neutrophilic Leucocytosis. 
Moist Double Cover-glass Specimen. 
Magnification 750 

The erythrocytes are normal in appearance. The 
white corpuscles, relatively increased in number as 
compared to the erythrocytes, are seen to be large 
polymorphonuclear cells with finely granulated proto- 
plasm, indicating that they are polymorphonuclear 
neutrophiles. Some show ameboid motion. 



60 



Plate VIII. Fig. 16 




mm 



PLATE IX 
Figure 17.— Neutrophilic Leucocytosis 



The same case. 

Figure 17.— Neutrophilic Leucocytosis. 
Stained Film. Magnification 330 

The red corpuscles show slight variations in color 
due to the slight anemia. Sixteen polymorphonuclear 
neutrophiles and one transitional are seen in the field. 
The blood platelets are somewhat increased in 
number. 



64 



Plate IX. Fig. 17 




1 



mm 



PLATE X 
Figure 18.— Eosinophilic Leucocytosis 



--— 



Eosinophilic Leucocytosis. The increase in the 
number of eosinophils in this type of leucocytosis is 
relatively less marked than the increase of neutro- 
phils in neutrophilic leucocytosis and corresponds 
approximately to the relative proportions in normal 
blood in which there are about 150 to 300 eosinophiles 
in 1 c.mm. The presence of 6 per cent, or more 
eosinophiles in the differential count constitutes an 
eosinophilia when the absolute count is correspond- 
ingly increased. This condition is noted chiefly in 
bronchial asthma, skin disease, helminthiasis and 
particularly in trichinosis. 

Male, 31 years old. Trichinosis. Total leucocyte count 18,000 
in c.mm. Differential count shows 49.6 per cent, eosinophiles or 
8,930 in 1 c.mm. 

Figure 18.— Eosinophilic Leucocytosis. 
Stained Film. Magnification 330 

Erythrocytes unchanged. Numerous leucocytes 
are seen in the field, the majority (17) of which are 
eosinophiles, which are easily identified though the 
granular stain is imperfect. Four neutrophiles are 
seen in the center and above these there are two 
lymphocytes and one transitional. 



68 






Plate X. Fig. 18 








PLATE XI 

Figure 19. — Neutrophilic Leucocytosis 
Figure 20. — Eosinophilic Leucocytosis 



Figure 19. — Neutrophilic Leucocytosis. 
Stained Film. Magnification 750 

The polymorphonuclear type of the cells indicates 
that they are neutrophils . The granulation of the 
protoplasm is denser than in normal blood, a change 
usually noted in leucocytosis. The blood platelets 
vary in size and are increased in number. 



The same case as Figure 18. 

Figure 20.— Eosinophilic Leucocytosis. 
Stained Film. Magnification 750 

The decided increase in the number of eosinophiles 
is evident. The cells are somewhat smaller than the 
usual eosinophile, and some show granulations on the 
nucleus. 



72 



Plate XL Figs. 19, 20 





PLATE XII 
Figure 21.— The Leucocytosis of Children 



! 



Girl, 3 years old. Chronic intestinal catarrh. Leucocytes 
14,000 in 1 c.mm. Differential count shows 48 per cent, lym- 
phocytes or 6,500 in 1 c.mm. 

Figure 21. — Leucocytosis in a Child. 
Stained Film. Magnification 330 

While a true neutrophilic leucocytosis may occur 
in children, the simultaneous increase in neutrophiles 




a. Polymorphonuclear Neutrophiles. 
6. Lymphocytes. 

c. Transitionals. 

d. Turk's irritation forms. 

77 






and in mononuclear forms particularly the lympho- 
cytes, is the most frequent type of leucocytosis. 

Atypical forms of leucocytes are frequently seen in 
these cases, such as neutrophiles with round nuclei, 
Turk's irritation forms, and myelocytes, their number 
serving as an index to the gravity of the disease. The 
red corpuscles show no particular change. 



78 



Plate XII. Fig. 21 







tmw: 



PLATE XIII 

Figure 22.— Blood Changes in Diphtheria 
Figure 23. — Lymphocytosis 



Child, 6 years old. Septic diphtheria of nose, fauces and larynx. 
Duration 8 days. Cutaneous hemorrhages. Blood examination 6 
hours before death shows: Hemoglobin, 100 per cent.; red cells', 
4,388,000; leucocytes, 72,000. 



Figure 22. — Stained Film. 

750 



Magnification 



In fatal cases of diphtheria in addition to the usual 
neutrophilic leucocytosis, numerous neutrophilic mye- 
locytes are found, while these are not noted in favor- 
able cases. Turk's irritation forms and mononuclear 
neutrophiles also may occur in the favorable cases, 
and have no particular significance, but the presence 
of myelocytes must always be regarded as an unfavor- 
able prognostic sign. 

Six neutrophilic leucocytes are seen in the field; to 
the right there is a small lymphocyte with scarcely 
visible protoplasm, toward the center a distorted 
transitional, and adjoining this there are two neu- 
trophilic myelocytes, their irregular outline due to 
pressure. The red corpuscles show evidences of 
some anemia. 



\ 






Male, 22 years old. Typhoid fever. 26th day. Hemoglobin, 80 
percent.; red cells, 4,510,000; leucocytes, 6,300. Differential Count: 
Neutrophiles, 38.5 per cent, or 2,400; lymphocytes, 53.8 per cent, or 
3,400; transitionals, 5 per cent.; eosinophiles, 2.4 per cent.; baso- 
philes, none; irritation forms, 0.3 per cent. 

Figure 23. — Lymphocytosis. Stained 
Film. Magnification 750 

Lymphocytosis consists of an increase in the relative 
percentage as well as in the actual number of normal 
lymphocytes, which are derived in large numbers 

83 






m 



from lymph glands by virtue of pathological change 
or stimulus. The condition is observed in whooping 
cough, rickets, syphilis and typhoid convalescence, 
and follows injections of tuberculin. 

In the illustration, the red cells show pale centers 
owing to diminished hemoglobin. Three lympho- 
cytes, and one neutrophile practically without gran- 
ules, are seen in the field. The lymphocytes all 
belong to the large type, and one shows slight acido- 
philic granulation of its protoplasm. 






84 



Plate XIII. Figs. 22, 23 




I 







THE RED CORPUSCLES 

OF 

THE HUMAN BLOOD 

AND 

THE BLOOD PLATELETS 



PLATE XIV 



FIGURES 24-26 



PLATE XIV 

Figure 24. — Erythrocytes 
Figure 25. — Erythroblasts 
Figure 26.— Blood Platelets 









mm. 



Figure 24.— Erythrocytes. Magnification 

750 

Normal Erythrocytes are round disks with an aver- 
age diameter of 7 to 7 J microns, the margin often 
staining deeper than the center. 

Microcytes are abnormally small erythrocytes, 
round or deformed, with a normal or pale hemoglobin 
tint. They are to be considered degeneration forms. 

Macrocytes are abnormally large erythrocytes, 
usually quite round, frequently polychromatophilic, 
and rarely showing a uniform hemoglobin tint. 
They represent preliminary stages of the normal 
erythrocyte. 

Poikilocytes are deformed erythrocytes, usually 
bottle or pear shaped, and often very irregular. The 
hemoglobin content is always more or less diminished. 
They are considered degeneration forms which have 
lost their normal contour on account of lessened 
resistance. 

Figure 25. — Nucleated Red Corpuscles 
(Erythroblasts). Magnification 750 

Erythroblasts represent preliminary stages of 
normal red blood cells, their appearance in the peri- 
pheral blood indicating increased activity of the bone 
marrow in the formation of erythrocytes. 

Normoblasts are of the same size as erythrocytes 
and have a relatively large round nucleus showing 
radiating or segmented structure. The cell body of 
the mature normoblast has a pure hemoglobin tint, 
but the younger cells are frequently polychromato- 
philic. 

90 



Microblasts are characterized by their small size, 
and show degenerative changes of the cell body 
(poikilocytosis), and pycnotic nuclei of dense struc- 
ture, which stain deeply. Free microblast nuclei are 
sometimes seen, and are easily differentiated from 
other structures by their small size and dark blue 
color. 

Megaloblasts are two or three times the size of 
normoblasts, and the older forms have a relatively 
small nucleus. Polychromatophilic megaloblasts are 
not uncommon, and present large, loose structured 
nuclei, poor in chromatin. The megaloblast origi- 
nates from a pathologically altered regeneration of 
the blood with a reversion to the embryonic type. 

Nuclear Division Figures of Erythroblasts. Ami- 
totic (direct) division is more frequently observed in 
megaloblasts than in normoblasts. Attention to the 
hemoglobin or polychromatophilic stain of the cell 
body differentiates these cells from lymphocytes of 
similar appearance, in which the nucleus may also 
undergo amitotic division, but the cell body is always 
basophilic (blue). 

Mitotic division is rarely observed in the leukemias 
and in pernicious anemia. The nuclear division 
figures are often large and beautifully marked with 
more or less distinct diaster formation. The cell 
body is still slightly basophilic and usually shows 
basophilic granulation. 



Figure 26.— Blood Platelets. Magnifica- 
tion 750 

These are blood elements of various shapes, which 
range in size from some scarcely visible, to others 
with a diameter of 10 microns. The smallest forms 
appear as pale, sharply circumscribed disks, which 
may have crenated margins, and show a nuclear sub- 
stance also varying in size and often with only few 
chromatin granules. 

91 



m* 



The larger forms are oval or rod-shaped, with 
abundant nuclear substance of a dark chromatin 
tint. These may show processes varying in length 
up to twice the diameter of the platelet, which also 
contain chromatin (see Fig. 40). 

Ordinarily, the platelets occur in small groups, or 
singly, but in the blood of persons having malignant 
tumors they may be found aggregated in large 
numbers. 

The origin and the significance of the platelets are 
still obscure. They are usually found increased in 
number during, and after, all conditions associated 
with leucocytosis, or with disintegration of leucocytes. 
They are enormously increased in myelogenous 
leukemia. 

The practical method of determining their number 
is by means of an approximate estimate in the stained 
film. 



92 



r 



2+ 



Plate XIV. Figs. 24, 25, 26 



r. 



25 



• 



© • 



• 



i 

oo 



26 






s 



dgN >A 



■ttdpyfatSMg 






;v8 ••' 



THE ANEMIAS 

PLATES XV-XXII FIGURES 27-41 






PLATES XV- XXII 



, 



Figures 27-41.— The Anemias 

Polychromatophilia 

This term indicates a changed behavior of the 
erythrocytes toward the stain. Polychromatophilic 
erythrocytes show a mixed staining quality varying 
from an almost pure eosin to a dirty blue or violet. 
In the more marked instances the corpuscles appear 
spotted as if occupied by a basophilic stroma. 

The condition is found in all stages of development 
of the immature erythrocyte, particularly in the 
nucleated cells, and those showing nuclear division 
figures. It is, therefore, regarded as a sign of imma- 
turity of the red corpuscle, and consequently a 
symptom of increased regeneration. 



97 






WW 



PLATE XV 

Figure 27. — Karyolytic Forms of Erythro- 
blasts 

Figure 28. — Polychromatophilic Erythro- 
cytes 

COfC 



I 



Figure 27.— Karyolytic Forms of Erythro- 
blasts. Magnification 750 

These are often present in large numbers in cases 
of progressive severe anemia, and particularly in the 
anemia of congenital syphilis in children. 

The nuclei are extremely varied in appearance and 
show budding and constrictions with pycnotic seg- 
ments. A small nucleus, poor in chromatin, is some- 
times seen in a polychromatophilic cell, apparently 
a remnant of an original nucleus which has under- 
gone dissolution. 



Child, 2% years old. Anemia gravis with congenital syphilis. Red 
cells, 1,564,000; leucocytes, 14,000. 

Figure 28. — Polychromatophilic Erythro- 
cytes. Stained Film. Magnification 
750 

The erythrocytes show moderate variations in size 
and shape, with both slight and pronounced poly- 
chromatophilia (see Fig. 41). A megaloblast in 
process of division, with polychromatophilic cell 
body, is seen above, and on the right there is a lymph- 
ocyte with the usual blue stained protoplasm. 



100 






Plate XV. Figs. 27, 28 








IMMJ 






PLATE XVI 

Figure 29.— Basophilic Granulation 
Figure 30.— Lead Poisoning 









Basophilic Granulation 

In this change the normal erythrocyte, or more 
frequently the polychromatophilic erythrocyte, con- 
tains granules which take a basic stain. The granules 
vary in size ; some are scarcely visible and others are 
as large as the neutrophilic granules in leucocytes. 
Poikilocytes and microcytes occasionally contain 
unusually large angular granules. They also vary 
in number, sometimes rilling the entire cell. 

Basophilic granulation is also found in nucleated 
red cells and in those presenting nuclear division 
figures. Polychromatophilia being considered an 
indication of immaturity, the designation of an 
accompanying basophilic granulation as "granular 
degeneration" does not seem justified, but as yet no 
definite opinion is possible. It is observed in all 
types of anemia and particularly in cases of lead 
poisoning. 

Figure 29. — Basophilic Granulation. Stained 
Film. Magnification 750 

Composite picture of specimens from a case of 
chronic lead poisoning. The varieties of basophilic 
granulation and its combination with polychroma- 
tophilia are the noteworthy features. 



Male, 25 years old. Painter, suffering from chronic lead poisoning. 

Figure 30 — Lead Poisoning. Stained Film. 
Magnification 750 

Granular erythrocytes are invariably present in 
cases of lead poisoning. They are more numerous 

105 



, 



^ 



in this condition than in any other disease, and the 
blood picture is practically pathognomonic. 

The erythrocytes show slight variations in size and 
color. In some the color is limited to the margins 
and slight polychromatophilia is apparent. Nine 
red cells which have more or less marked basophilic 
granulation are seen in the field. 



106 



Plate XVI. Figs. 29, 30 





PLATES XVII -XIX 






Figures 31-36. — Secondary Anemia 

Secondary anemia includes all the anemic condi- 
tions developing in the course of different diseases 
which are not based on the primary involvement of 
the blood-making organs. The group includes all 
affections leading to loss of blood, malnutrition and 
cachexia (gastric and intestinal ulcers, animal para- 
sites, infectious diseases, malignant tumors). In 
order to study the morphology of the red corpuscles 
in primary as well as secondary anemia, it is essential 
to examine fresh specimens, as the changes noted in 
stained films are often artefacts. 






109 



PLATE XVII 



Figure 31.— Acute Anemia 
Figure 32.— Chronic Anemia 



Secondary Anemia. Acute Form 

Soon after a severe hemorrhage there is a diminu- 
tion in the number of red corpuscles and in the 
amount of hemoglobin, due to a transfer of fluids 
from the tissues into the blood. Regenerative phe- 
nomena are soon noted by the presence of polychro- 
matophilia, macrocytes and normoblasts, which im- 
mature forms are usually deficient in hemoglobin. 
The number of red cells increases rapidly, while the 
increase in hemoglobin content is slower. 



Female, 45 years old. Ulcer of the stomach. Hemoglobin, 35 per 
cent.; red corpuscles, 1,960,000; leucocytes, 6,300 in 1 cmm. 

Figure 31. — Acute Anemia. Stained Film. 
Magnification 750 

The erythrocytes are further apart in the stained 
specimen, owing to the dilution of the blood. The 
lack of uniformity in size is due to the presence of 
numerous polychromatophilic macrocytes, and not 
to changes in the normal cells. A polychromatophi- 
lic normoblast is seen above and a lymphocyte be- 
low. Several blood platelets are also present. 

Secondary Anemia. Chronic Form 

In addition to the changes noted above, these 
cases also show variations in the shape of the red 
cells and a more or less pronounced diminution in the 
amount of hemoglobin. The red cells may simply 
show decided loss of hemoglobin, without polychro- 
matophilia. An absence of immature erythrocytes 
in cases of secondary anemia justifies a suspicion of 

113 



mm 



paralysis of function of the bone marrow, as far as 
formation of erythrocytes is concerned. The more 
numerous the immature red cells, the greater the 
functional activity of the blood-forming organs. 
When the bone marrow is suddenly called upon to 
supply a marked deficit, there may be a transitory 
flooding of the circulation with many nucleated cells. 



Male, 54 years old. Carcinoma of stomach. Hemoglobin, 35 per 
cent.; red cells, 1,336,000; leucocytes, 13,100 in 1 c.mm. 

Figure 32.— Chronic Anemia. Stained 
Film. Magnification 750 

The red cells show the characteristic evidences of 
secondary anemia, i.e., diminished and uneven 
hemoglobin distribution, polychromatophilia, changes 
in size and shape of corpuscles. 



114 



Plate XVII. Figs. 31, 32 







ill 


1 


1 1 





PLATE XVIII 

Figure 33. — Chronic Anemia 

Figure 34. — Infantile Hereditary Syphilis 



^^ 



Figure 33.— Chronic Anemia. Stained Film. 
Magnification 330 

The same changes are noted as in Fig. 32, and the 
pathological condition is particularly apparent when 
compared with Fig. 3, which represents normal blood. 

Two neutrophiles are seen in the field, with a 
normoblast above and numerous blood platelets. 

Anemia in Children having Congenital Syphilis 
In well marked cases the changes in the red cells 
are sufficiently pronounced to make this one of the 
cardinal symptoms. In addition to a leucocytosis, 
numerous bone-marrow cells are found, which justify 
the belief that the bones are also involved in the 
pathological lesion and that the presence of these 
cells is the result of direct irritation of the bone 
marrow by the local syphilitic process. Neutro- 
philic and eosinophilic myelocytes and immature 
lymphocytes are present, together with a large number 
of nucleated red cells, microblasts, normoblasts and 
frequently megaloblasts and nuclear division figures. 
The large number of karyolytic forms is noteworthy 
(see Fig. 27). The red cells appear deficient in 
pigment, but poikilocytosis, polychromatophilia, and 
basophilic granulation are not common. The num- 
ber of erythrocytes is always considerably diminished, 
with a corresponding reduction in the amount of 
hemoglobin. 

117 



mm 



Child, l£ years old. Hereditary syphilis. Red cells, 2,500,000; 
leucocytes, 18,000 in 1 c.mm. 

Figure 34. — Infantile Hereditary Syphilis. 
Stained Film. Magnification 750 

The specimen contained numerous nucleated rea 
cells their number exceeding the total leucocyte 
count. The stained film of blood, obtained after 
death, shows some disintegrating cells. 




a. Normoblasts and Megaloblasts. Some of the latter unusually large, with 

more or less basophilic protoplasm, and one or more nuclei poor in chro- 
matin. 

b. Karyolytic Forms of Normoblasts and Megaloblasts. 

c. Lymphocytes. One with divided Nucleus. 

d. Granular and Non-granular Bone marrow Cells. 



118 



Plate XVIII. Figs. 33, 34 











PLATE XIX 

Figure 35. — Secondary Anemia. Chronic 
Form 

Figure 36.— Crenated Red Corpuscles 



Secondary Anemias 
Same case as Figure 32. 

Figure 35. — Chronic Secondary Anemia. 
Fresh Double Cover-glass Specimen. 
Magnification 750 

The pale tint of the red cells indicates their loss 
of hemoglobin, especially when compared with nor- 
mal blood. 

The varied outline of red corpuscles is most appar- 
ent in the fresh specimen, but an opinion as to their 
size requires experience. Pear-shaped and bottle- 
shaped cells, and multilobular poikilocytes are pres- 
ent. A microcyte is seen in the center of the field. 
The two humped and oblong red cells are changes, 
due presumably to evaporation, the details of which 
are seen in the following picture. 

Figure 36.— Crenated Erythrocytes. Fresh 
Double Cover-glass Specimen. Mag- 
nification 750 

The illustration shows the crenated forms of red 
cells, formerly believed to be the same thing as 
poikilocytes. The characteristic changes are evident. 

121 



ji 






The crenated forms may be observed in any 
specimen of fresh blood which has evaporated or 
suffered mechanical injury. In fact the occurrence 
of a few of these near the margin can scarcely be 
prevented in the fresh specimens, though carefully 
prepared. 

Crenation within a few seconds of all the red 
corpuscles in a properly made specimen is pathologi- 
cal, and must be considered an evidence of lessened 
resistance on the part of the erythrocytes. Error is 
prevented by observing this in several successively 
prepared specimens. Normal blood does not show 
this change to any extent until after the lapse of from 
thirty minutes to several hours. 



122 



Plate XIX. Figs. 35, 36 





PLATES XX XXII 

Figures 37-41. — Primary Anemias 

The Primary Anemias 

The characteristic feature in the diagnosis of 
primary anemia, is the presence of anemic conditions, 
varying in kind and degree, with an absence of all 
other causative diseases. In chlorosis and certain 
anemias of childhood, nothing but an affection of 
the blood itself has as yet been demonstrated, whereas 
in pernicious anemia the blood-forming organs are 
the seat of the lesion. 

The anemias of childhood present no specific or 
particularly characteristic changes in the blood, but 
in chlorosis, as well as in pernicious anemia, definite 
evidences are found, which are characteristic of the 
one or the other condition. 



125 



^ 



PLATE XX 

Figure 37. — Pernicious Anemia 
Figure 38. — Chlorosis 



Female, 63 years old. Pernicious Anemia. Hemoglobin, 35 per 
cent.; red cells, 1,032,000; leucocytes, 16,000 in 1 c.mm. Marked 
polychromatophilia and pronounced variations in the size of the red 
cells. Normoblasts and megaloblasts are present. 

Figure 37. — Pernicious Anemia. Fresh 
Double Cover-glass Specimen. Mag- 
nification 750 

Most of the red cells are deficient in hemoglobin, 
but some have a normal color. The uneven dis- 
tribution of hemoglobin is always apparent. The 
pronounced difference in the size of the corpuscles is 
noteworthy; about half of them are megalocytes, and 
there are also many microcytes, some so small that 
they are difficult to distinguish from blood platelets 
in the fresh specimen. 

Poikilocytosis was not a pronounced feature in this 
case of pernicious anemia in which the diagnosis was 
verified by autopsy. This change is evidently not 
present to the same degree in every case, and probably 
depends to some extent on the duration of the disease. 



127 



Female, 28 years old. Chlorosis. Hemoglobin, 50 per cent.; red 
cells, 4,320,000; leucocytes, 9,600 in 1 c.mm. 

Figure 38.— Chlorosis. Fresh Double Cover- 
glass Specimen. Magnification 750 

In chlorosis, even the fresh blood differs in several 
essential features from that of secondary anemia or of 
pernicious anemia. Primarily, the erythrocytes show 
a uniform decided diminution in blood-coloring mat- 
ter, which is very apparent in severe cases. Poikilo- 
cytosis is not as pronounced in severe chlorosis as 
it is in severe secondary anemia, and the marked 
difference in the size of the corpuscles seen in perni- 
cious anemia, is absent. In cases of severe hydremia 
a uniform increase in the size of a large number of 
erythrocytes is frequently observed. When the chlor- 
osis is not pronounced, no particularly characteristic 
changes can be made out in a fresh specimen. 

Figure 38 shows a specimen of blood from a case 
of chlorosis. The red cells are practically uniform in 
size and very pale in color. Few pear-shaped poiki- 
locytes are present. The erythrocytes, viewed later- 
ally, show a light zone which is probably a reflection. 



128 



Plate XX. Figs. 37, 38 





PLATE XXI 
Figures 39-40.— Chlorosis. 



Girl, 26 years old. Severe Chlorosis. Hemoglobin, 35 per cent.; 
red cells, 4,000,000; lymphocytes, 4,400 in 1 c.mm. 

Figure 39.— Chlorosis Stained Film. 
Magnification 750 

In chlorosis the diminution in the amount of 
hemoglobin is much greater than in the number of 
red corpuscles, and this characteristic loss of coloring 
matter is apparent in all the corpuscles by the narrow 
stained rim as shown in the illustration. There is 
only a slight difference in the size of the cells, but 
poikilocytosis is evident. The platelets are increased 
in number. A lymphocyte is seen on the. right. 



Female, 26 years old. Convalescing Chlorosis. Hemoglobin, 90 
per cent.; red cells, 4,600,000; leucocytes, 7,200 in 1 c.mm. 

Figure 40. — Chlorosis. Stained Film. 
Magnification 750 

The specimen shows the decided and uniform in- 
crease in the amount of hemoglobin in the corpuscles 
during convalescence, but the pale centers indicate 
that this is not yet quite normal. Few poikilocytes 
are present. 

The flagella-like processes of the platelets are seen 
in this specimen. 



132 



Plate XXI. Figs. 39, 40 





PLATE XXII 
Figure 41.— Pernicious Anemia 

Pernicious Anemia 

In cases of pernicious anemia the blood as a rule 
presents a characteristic series of changes not noted 
in any other disease. The diminution in the number 
of red corpuscles is out of proportion to the loss of 
hemoglobin. In making the red cell count, care 
should be exercised not to overlook the numerous 
microcytes usually present. The disproportionate 
loss of red cells and hemoglobin is explained by the 
fact that, while very pale corpuscles are seen, there 
are also many which contain a normal amount of 
blood pigment. Decided polychromatophilia is in- 
variably noted, and basophilic granulation is common. 
Pronounced poikilocytosis seems to develop only in 
the protracted cases. The presence of megalocytes 
and megaloblasts constitutes a particularly charac- 
teristic feature, and their occurrence is explained by a 
megaloblastic transformation of the bone marrow as 
far as the formation of red cells is concerned. Mi- 
toses of erythroblasts may also be found. These 
evidences of disintegration and abnormal regener- 
ation of the blood are not found in chlorosis or second- 
ary anemia. 

The leucocyte count in pernicious anemia varies 
considerably. Leucopenia is an unfavorable prog- 
nostic sign. While neutrophilic leucocytosis is noted 
in the course of improvement, it may also be indicative 
of inflammatory complications. The presence of 
myelocytes and Turk's irritation forms is not uncom- 
mon. 

135 



Same case as Figure 37. Duration of disease four 
weeks. 

Figure 41.— Pernicious Anemia. Stained 
Film. Magnification 750 

The decided polychromatophilia and the slight 
poikilocytosis are apparent and probably explained 
by the severity and short duration of the case. Lack 
of uniformity in the distribution of hemoglobin is 
also evident, some cells being very pale, while others 
seem to contain an excessive amount of blood pigment. 

Two megaloblasts with pycnotic nuclei are seen 
above, to the right, and in the center there is a 
megaloblast with a large nucleus poor in chromatin 
and a basophilic cell body. A Turk's irritation form 
is seen immediately beneath the latter, and these two 
cells show a striking resemblance. A megaloblast in 
process of mitotic division is also seen, and to the 
right a polymorphonuclear neutrophile. 



136 



Plate XXII. Fig. 41 




THE LEUKEMIAS 

PLATES XXIII -XXXVII FIGURES 42-58 



PLATES XXIII -XXXVII 

Figures 42-58.— The Leukemias 

The Leukemias 

The diagnosis of leukemia is based on the demon- 
stration of a permanent increase in the number of 
white corpuscles in the blood, a large percentage of 
which are bone marrow cells or abnormal leucocytes. 
This statement applies to myelogenous leukemia as 
well as to lymphatic leukemia, and for the present 
this classification seems desirable, as it is based on 
the condition of the blood. Further subdivisions do 
not seem indicated as yet, particularly as almost 
every case of leukemia presents individual charac- 
teristics. These may undergo pronounced change 
in the course of the disease, by variations in the 
relative proportion of the different varieties of cells, 
as well as by the disappearance of some and sudden 
appearance of other types. 

All cases show a more or less marked anemia, 
which may present all the characteristics of a perni- 
cious anemia, but some are seen, with several hundred 
thousand leucocytes in a cubic millimeter, without 
apparent change in the red cells. The severity of 
the disease is appreciably dependent on the condition 
of the red cells. 

A detailed description of the changes in the blood 
in the different forms of leukemia will be found in 
connection with the following illustrations. 



141 



PLATE XXIII 
Figure 42. — Myelogenous Leukemia 



Female, 23 years old. Myelogenous Leukemia. Hemoglobin, 65 
per cent.; red cells, 3,200,000; leucocytes, 337,000 in 1 c.mm. 

Figure 42. — Myelogenous Leukemia. Fresh 
Double Cover-glass Specimen. Mag- 
nification 750 

The decided increase in the number of leucocytes 
is evident. In this connection it is well to recall that 
some cases of leukemia may show comparatively low 
leucocyte counts, for example, 10,000 in 1 c.mm., 
whereas a leucocytosis of 50,000 or more may exist 
for a considerable period. Consequently the count 
alone is not sufficient for diagnosis. As considerable 
practice is necessary to differentiate the various types 
of leucocytes in a fresh unstained specimen, and some 
cannot be recognized in this way at all, the dried and 
stained films are preferable for the purpose. 

The red cells show no essential change. The fol- 
lowing four types of leucocytes can be recognized in 
the illustration: 

a. Polymorphonuclear finely granular forms, noted 
in Fig. 16, are neutrophiles. 

b. Cells of the same size with round or lobulated 
nuclei and coarse refractive granulation are eosino- 
philic myelocytes or eosinophiles. 

c. Larger and lighter cells with round nuclei and 
finely granular protoplasm are bone marrow cells, 
which can be more accurately classified in the stained 
specimen. 

d. Small leucocytes of different forms which also 
cannot be classified in the unstained specimens. 

The greater the variety of leucocytes present, the 
more difficult the classification, in unstained speci- 
mens. 

144 



Plate XXIII. Fig. 42 




PLATE XXIV 
Figures 43-44. — Myelogenous Leukemia 



Male, 62 years old. Myelogenous Leukemia. Blood very concen- 
trated. Hemoglobin, 105 per cent.: red cells, 5,184,000; leucocytes, 
59,300 in 1 cmm. 

Figure 43. — Myelogenous Leukemia. Fresh 
Double Cover-glass Specimen. Mag- 
nification 750 

The addition of a few drops of an aqueous solution 
of gentian violet to the diluting fluid differentiates 
the leucocytes somewhat (compare Fig. 42), but is 
not sufficient for the proper classification and recog- 
nition of the pathological forms. The red cells show 
but little change in shape and size. A group of blood 
platelets is seen in the center, on the right a poly- 
morphonuclear neutrophile, on the left two granular 
bone-marrow cells and above a lymphocyte. 



The same case. 

Figure 44. — Myelogenous Leukemia. 
Stained Film. Magnification 750 

The various characteristics of the different varieties 
of leucocytes are apparent in the stained specimen. 
In the fresh specimen, for example, it is impossible 
to distinguish the neutrophilic myelocyte from the 
basophilic mononuclear, as the vesicular structure 
of the latter looks just like the fine granulation of the 
former. 

The red cells show evidence of considerable anemia. 
While undue concentration of the blood has given 
normal hemoglobin and red cell figures as above, the 
anemic changes of the red cells are made apparent 
in the stained specimen by differences in size, irregu- 

149 



larity in shape, polychromatophilia and the presence 
of normoblasts. A megaloblast is seen above and 
a normoblast below, both showing polychromato- 
philia. Two polymorphonuclear neutrophiles and 
blood platelets are also present. The other cells will 
be described later. 



150 



Plate XXIV. Figs. 43, 44 





PLATES XXV XXVIII 

Figures 45-49. — Chronic Lymphatic 
Leukemia 

Chronic Lymphatic Leukemia 

Chronic lymphatic leukemia is characterized by 
the presence in the blood of varying numbers of 
abnormal lymphocytes, usually of the small, but 
occasionally of the large type. The absolute counts 
are generally high, ranging from 50,000 to 1,000,000 
in 1 c.mm. The relative percentage of these lym- 
phocytes is also high, ranging from 95 to 99 per cent, 
of the leucocytes, there being an absolute decrease in 
the other varieties. 

The appearance of the blood is not complex, and 
is absolutely characteristic of the condition. 

The red corpuscles are usually in fair condition, 
and only show extensive change in the advanced and 
terminal stages of the disease, when there is a de- 
crease in their number and a corresponding loss in 
the amount of hemoglobin. 

The blood platelets are slightly, if at all, increased 
in numbers. 



153 



PLATE XXV 
Figure 45.— Chronic Lymphatic Leukemia 



Male, 44 years old, sick for one year. Multiple swellings of lym- 
phatic glands. Spleen enlarged, and extending to the median line. 
Progressive anemia for the past three months. Duration of disease 
eighteen months. 

A complete examination of the blood could not be 
made, but the stained film justifies a diagnosis of 
chronic lymphatic leukemia. 

Figure 45. — Chronic Lymphatic Leukemia. 
Stained Film. Magnification 330 

The increase in the number of lymphocytes is such 
that there are more white than red cells. The 
lymphocytes all appear of approximately the same 
size and show a very narrow margin of protoplasm, 
barely visible in some. There are a few somewhat 
larger lymphocytes with a lighter colored nucleus. 
An abnormal segmentation of the nuclei is noted 
which is foreign to lymphocytes in normal blood. 
(For details see Fig. 47.) 

The red cells show no change except diminished 
hemoglobin content. 



156 



Plate XXV. Fig. 45 




PLATE XXVI 

Figures 46-47.— Chronic Lymphatic 
Leukemia 



Chronic Lymphatic Leukemia. For detailed con- 
dition of the blood see description of Fig. 48. 

Figure 46.— Chronic Lymphatic Leukemia. 
Fresh Double Cover-glass Specimen. 
Magnification 750 

The nuclei of the lymphocytes are stained light 
blue by the addition of a drop of aqueous solution of 
gentian violet to the diluting fluid. Nothing ab- 
normal is apparent in the lymphocytes of this wet 
specimen, except that they appear a little larger than 
those in normal blood. A polymorphonuclear neu- 
trophil is seen on the right. The red cells show a 
normal amount of coloring matter. 

The same specimen as in Fig. 45. 

Figure 47.— Chronic Lymphatic Leukemia. 
Stained Film. Magnification 750 

A thin smear is essential in order to recognize the 
abnormal features of the lymphocytes in chronic 
lymphatic leukemia, as they differ considerably from 
the small lymphocytes of normal blood. They are 
larger and have apparently segmented nuclei, poor 
in chromatin, which practically fill the cells and 
lend the impression of immaturity. There is 
a narrow margin of protoplasm, sometimes barely 
visible. Acidophilic granules cannot be demon- 
strated. 

These cells must be considered immature lympho- 
cytes representing a definite stage in the development 
of the lymphocytes of normal blood. 

The red corpuscles are somewhat deficient in 

hemoglobin. 

160 



Plate XXVI. Figs. 46, 47 








PLATE XXVII 

Figure 48. — Chronic Lymphatic 
Leukemia 



Male, 38 years old. For past eighteen months progressive glandu- 
lar swellings in the neck and both axillae. At present all superficial 
glands are palpable and about the size of a plum. Spleen 10 X 7 cm. 
The blood has normal appearance and concentration. Hemoglobin, 
115 per cent.; red cells, 4,928,000; leucocytes, 79,000 in 1 c.mm. 
Differential count: Polymorphonuclear neutrophiles, 5.2 per cent. 
(4,090); lymphocytes, 94.2 per cent. (74,390); transitionals, 0.4 per 
cent. (370); eosinophiles, 0.2 per cent. (150). 

Diagnosis: Chronic Lymphatic Leukemia. 



Figure 48. — Chronic Lymphatic Leukemia. 
Stained Film. Magnification 330 

The increase in the number of lymphocytes is not 
nearly as great in this case as in Fig. 45. Most of 
the cells show the characteristics described above. 
A few of the lymphocytes have a larger amount of 
protoplasm, and others show an irregular or notched 
nucleus. On the right is seen a nuclear figure, poor 
in chromatin, which looks like a flattened nuclear 
remnant, but really has a different significance, as 
seen in Fig. 49. 

The red cells are practically normal. The plate- 
lets are increased in numbers. 



164 



Plate XXVII. Fig. 48 




PLATE XXVIII 
Figure 49.— Chronic Lymphatic Leukemia 



Male, 56 years old. During the past four years he has had glandu- 
lar swellings on both sides of the neck, with periods of remission. 
Renewed swelling has been present for the past year with the addition 
of glandular enlargement in both axillae, in the inguinal folds, near the 
eyes and at the angle of the jaw. Spleen is considerably enlarged 
(24 X 16 cm.). Moderate cachexia. 

Hemoglobin, 105 per cent.; red cells, 5,176,000; leucocytes, 53,600 
in 1 c.mm. Differential count: Polymorphonuclear neutrophiles, 6.2 
per cent, or 3,400; lymphocytes, 92.7 per cent, or 50,000, of which 
16.5 per cent, or 8,900 are large fragile forms. Transitionals and 
eosinophiles, 0.55 per cent, each, or 300 each in 1 c.mm. 

Diagnosis : Chronic Lymphatic Leukemia. 



Figure 49. — Chronic Lymphatic Leukemia. 
Stained Film. Magnification 750 

In addition to the abnormal lymphocytes described 
above, almost every case of chronic lymphatic 
leukemia shows fragmentary nuclear structures poor 
in chromatin. The nucleus often has the appearance 
of being partially dissolved, and looks like a granular 
mass devoid of protoplasm. Well preserved cells 
of this type are rarely seen, justifying the inference 
that they are very fragile and non-resistant, or that 
they cannot exist in the peripheral circulation. 
Some of these resemble large lymphocytes, while 
others are like large homogeneous, slightly basophilic 
bone marrow cells. Their nuclei, poor in chromatin, 
are indented or lobulated, rarely showing nucleoli. 

These large cells must be considered as the large 
homogeneous bone marrow cells which enter the 
circulation at this stage of their development. 

In another case where the ordinary type of small 
lymphocytes was usually present, the author noted 

169 



two short periods during which the blood contained 
large numbers of these "fragile cells," which would 
seem to indicate a specific irritation of the bone 
marrow. 

When this large type of cell occurs in chronic 
lymphatic leukemia, it seems reasonable to conclude 
that there is also a lesion of the bone marrow. 



170 



Plate XXVIII. Fig. 49 




PLATES XXIX XXXV 

Figures 50-56.— Myelogenous Leukemia 

i 

Myelogenous Leukemia 

Contrary to the rather uniform changes in the 
blood noted in chronic lymphatic leukemia, the cases 
of myelogenous leukemia present a most varied and 
sometimes confusing picture. All types of leucocytes 
found in normal blood are present, in addition to 
myelocytes in different stages of development. The 
leucocyte count is always high, ranging usually be- 
tween 200,000 and 2,000,000, and figures below 
50,000 in 1 c.mm. are rare. 

The leucocyte count may recede several thousand 
as the result of intercurrent febrile disorders (sepsis, 
tuberculosis, etc.), or therapeutic measures (arsenic, 
X-ray, etc.), but myelocytes are invariably present 
in the peripheral circulation, even under these cir- 
cumstances, and the diagnosis of myelogenous 
leukemia is evident. 

While there is an increase in the actual number of 
each variety, the polymorphonuclear neutrophile is 
the normal cell to which this applies chiefly. The 
myelocytes also show high figures, and several hun- 
dred thousand may be present in 1 c.mm. One or 
other type of these bone marrow cells usually pre- 
dominates during the entire course of the disease, 
and the different types are rarely present in equal 
numbers. 

The diagnosis of myelogenous leukemia can be 
made on examination of the blood, even if the leuco- 

173 



cyte count is not excessive. In addition to the 
leucocyte increase, these cases invariably show 
changes in the red cells which are, however, not as 
pronounced as in acute leukemia. The blood platelets 
are always decidedly increased in number. 

The seven plates on the following pages illustrate 
four types of myelogenous leukemia, each charac- 
teristic on account of the predominance of special 
cellular types. 



174 



PLATE XXIX 
Figure 50.— Myelogenous Leukemia 



Female, 25 years old. Has been ill for the past three years, and 
under treatment for leukemic enlargement of the spleen for two years. 
Occasional periods of improvement, due to administration of arsenic. 
On admission to hospital rather pale and emaciated. Has a greatly 
enlarged spleen extending to the symphysis, and numerous cutaneous 
thrombi. 

The blood is thin and coagulation is retarded. Hemoglobin, 70 
per cent.; red cells, 3,300,000; leucocytes, 390,000 in 1 c.mm. Differ- 
ential count: Neutrophiles, 43.07 per cent., or 168,000; lymphocytes, 
1.88 per cent., or 7,000; transitionals, 2.31 per cent., or 9,000; eosino- 
philes, 3.46 per cent., or 13,500; basophiles, 12.17 per cent., or 47,500; 
myelocytes, 37.11 per cent., or 145,000 in 1 c.mm. 

Diagnosis: Myelogenous Leukemia. 

Figure 50. — Myelogenous Leukemia. 
Stained Film. Magnification 330 

The difference between the appearance of the 
blood in this disease and that in chronic lymphatic 
leukemia (Fig. 45) is immediately apparent. The 
number of leucocytes seems much greater than in the 
most severe leucocytosis. The neutrophiles, iden- 
tified by their polymorphonuclear character, are in 
excess of other forms. Normal lymphocytes are not 
present in this field. Eosinophiles and basophiles 
are increased in number. The presence of leuco- 
cytes which do not occur in normal blood is the 
striking feature in the picture, although a low power 
is used. These are eosinophilic myelocytes and 
large cells with round nuclei and considerable proto- 
plasm which demand a higher power for close study. 
The red corpuscles are pale; a normoblast is seen 
above and another below toward the left. Blood 
platelets are increased in number. 

176 



Plate XXIX. Fig. 50 




PLATE XXX 
Figure 51.—- Myelogenous Leukemia 



The same specimen. 

Figure 51. — Myelogenous Leukemia. 
Stained Film. Magnification 750 

The diversity of the cellular forms in the specimen 
was such that all could not be included in this 
composite picture. 




a. Polymorphonuclear neutrophile. b. Eosinophile. c. Basophile, includ- 
ing abnormal forms usually abundant in myelogenous leukemia, d. Eosino- 
philic myelocytes. These cells vary considerably in size, have large, pale 
round or indented nuclei, which are frequently indistinct. The protoplasm is 
basophilic and usually distended with eosinophilic granules. Some basophilic 
granules may be found mixed with the eosinophilic in the unusually small cells 
of this type. e. Homogeneous mononuclears with basophilic protoplasm and 
nuclei in different stages of development showing nucleoli, f. Homogeneous 
mononuclears with basophilic protoplasm showing slight neutrophilic granula- 
tion, g. A more mature lymphocyte, h. Disintegrating eosinophile. i. Nu- 
clear remnant with nucleolus and nuclein strands, k. "Fragile Form." 

181 



A normoblast is present (1). Polychromatophilia 
and basophilic granulation in red cells can be seen. 
There are also many blood platelets. 

No neutrophilic myelocytes present. 



182 



Plate XXX. Fig. 51 




PLATE XXXI 
Figure 52. — Myelogenous Leukemia 

Myelogenous Leukemia 

The same case after the administration of arsenic 
and use of X-ray. Complicated by extensive tuber- 
culous lesion of both lungs. Two days before death. 

Hemoglobin, 55 per cent.; red cells, 2,344,000; leucocytes, 78,900 
in 1 cmm. Differential count: Polymorphonuclear neutrophiles, 
55,630, or 70.42 per cent.; lymphocytes, 9,270,. or 11.72 per cent.; 
transitionals, 2,780, or 3.52 per cent.; basophiles, 930, or 1.20 per 
cent.; myelocytes. 10,390, or 13.14 per cent. Of the latter, neutrophilic 
myelocytes, 6,490, or 8.20 per cent.; eosinophilic myelocytes, 190, 
or 0.24 per cent. ; immature stages of neutrophilic myelocytes, 3>710, 
or 4.70 per cent. 



Figure 52. — Myelogenous Leukemia. 
Stained Film. Magnification 750 

The character of the specimen has undergone a 
complete change. While a decided polymorpho- 
nuclear neutrophile leucocytosis is present, a distinct 

185 



leukemic composition is still apparent. The diminu- 
tion in the number of eosinophiles, myelocytes and 
basophilic cells as compared with the former specimen 
is noteworthy; these having been replaced by neu- 
trophilic myelocytes and immature forms of this 
type. This change is doubtless the result of the 
tuberculous infection, as it was not noted during 
the improvement caused by the administration of 
arsenic and the use of the X-ray. 







a. Polymorphonuclear neutrophiles some showing vacuoles of degeneration 
(compare Fig. 15). b. Neutrophilic myelocyte, c. Large mononuclears with 
basophilic protoplasm and numerous neutrophilic granules, d . Large homogen- 
eous mononuclears with neutrophilic protoplasm showing vacuoles, e. More 
mature lymphocyte. 

The number of blood platelets has diminished. 



186 



Plate XXXI. Fig. 52 




PLATE XXXII 
Figure 53. — Myelogenous Leukemia 

Myelogenous Leukemia 

Female, 23 years old. Has looked pale for past three and one- 
half years. Increasing enlargement of spleen for last eighteen months. 
At present there is decided pallor. Spleen extends 11 cm. to the 
right of median line. No glandular swellings. 

Hemoglobin, 65 percent.; red cells, 3,200,000; leucocytes, 337,000 
in 1 c.mm. Differential count: Polymorphonuclear neutrophiles, 
94,040, or 27.9 per cent.; myelocytes, 195,930, or 58.10 per cent.; 
basophiles, 39,190, or 11.7 per cent.; eosinophiles, 7,840, or 2.3 per 
cent. 

Diagnosis: Myelogenous Leukemia. 



189 



Figure 53. — Myelogenous Leukemia. 
Stained Film. Magnification 750 

The complex composition of the blood seen in 
Fig. 51 was never noted during the entire course of 
this case. In this specimen the leukemic change is 
shown by immature forms of myelocytes, instead of 
by typical eosinophilic and neutrophilic myelocytes. 
Formerly the case would have been called a myelogen- 
ous leukemia with lymphoid condition of the blood. 
The white corpuscles are noted in groups of twenty 
or thirty and have been distorted by pressure. 

The red cells show no particular change. 




a. Polymorphonuclear neutrophiles. b. Eosinophiles. c. Basophilic mye- 
locytes and basophiles. d. Mononuclears with more or less basophilic proto- 
plasm, e. Homogeneous mononuclears with neutrophilic protoplasm. /. Mono- 
nuclears with basophilic protoplasm and faint neutrophilic granulation. 

190 



Plate XXXII. Fig. 53 




PLATE XXXIII 
Figure 54. — Myelogenous Leukemia 



Myelogenous Leukemia 

The same case after treatment with arsenic and 
X-ray. 

Hemoglobin, 90 per cent.; red cells, 4,050,000; leucocytes, 14,000 
in 1 c.mm. Differential count: Polymorphonuclear neutrophiles, 
9,520, or 68 per cent.; myelocytes, 1,820, or 13 per cent.; basophiles, 
1,260, or 9 per cent.; eosinqphiles, 420 or 3 per cent.; lymphocytes, 
980, or 7 per cent. 




a. Polymorphonuclear neutrophiles. b. Basophiles. c. Homogeneous mon- 
onuclears with basophilic protoplasm, d. Mononuclears with basophilic 
protoplasm showing neutrophilic granulation. 

195 



Figure 54. — Myelogenous Leukemia. 
Stained Film. Magnification 750 

The condition of the blood shows decided improve- 
ment, and considerable search is necessary before 
two bone marrow cells are found in the same field, 
as in the illustration. Owing to the persistent high 
percentage of myelocytes the present condition must 
be considered a remission rather than a cure. The 
bone marrow cells present show no new types. 

The red corpuscles show moderately diminished 
hemoglobin content. Some of the blood platelets 
are very large. 



196 



Plate XXXIII. Fig. 54 




PLATE XXXIV 
Figure 55. — Myelogenous Leukemia 

Myelogenous Leukemia 

Male, 62 years old. Suffering for the past six months from general 
weakness and emaciation, with enlargement of the abdomen. Mod- 
erately anemic and cachectic. No glandular swellings. The spleen 
extends to the median line. Blood appears concentrated. Hemo- 
globin, 105 per cent.; red cells, 5,000,000; leucocytes, 55,200 in 1 
c.mm. Blood platelets much increased. Differential count: Poly- 
morphonuclear neutrophiles, 38,580, or 69.88 per cent.; lymphocytes, 
7,700, or 13.98 per cent.; transitionrJs, 390, or 0.71 per cent.; eosino- 
philes, 580, or 1.05 per cent.; basophiles, 580, or 1.05 per cent.; mye- 
locytes, 7,350, or 13.33 per cent. 

Numerous normoblasts, poikilocytes, polychromatophilia and baso- 
philic granulation of red cells. 

Diagnosis : Myelogenous Leukemia. 



Figure 55. — Myelogenous Leukemia. 
Stained Film. Magnification 750 

During the course of the disease this case con- 
stantly presented a condition of the blood known as 
"mixed cell leukemia." There is no valid reason 
for retaining the term in this case, or in the one 
described in connection with Fig. 53. In addition 
to neutrophilic myelocytes, there are cells represent- 
ing earlier stages of development of this type, namely, 
mononuclears with basophilic, homogeneous or gran- 
ular protoplasm. 

199 



This illustration and Fig. 53 show that all the 
forms of bone marrow cells need not necessarily be 
present in every case of myelogenous leukemia. 
Many specimens were examined, and not a single 
eosinophilic myelocyte found. As these cells develop 
from the basophilic myelocytes, it was not surprising 
to find comparatively few basophilic myelocytes and 
basophiles. 

Subsequent developments in this case could not 
be followed, as the patient returned to his home. 




a. Polymorphonuclear neutrophile. b. Immature lymphocyte, c. Neu- 
trophilic myelocytes, d. Mononuclears with more or less marked granular 
protoplasm, e. Large mononuclears with homogeneous basophilic protoplasm. 
/. Normoblast. 



Red cells show no essential change. Blood plate- 
lets are increased. 



200 



Plate XXXIV. Fig. 55 







PLATE XXXV 
Figure 56. — Myelogenous Leukemia 

Myelogenous Leukemia 

Female, 53 years old. Confined to bed for past six months. Ex- 
treme pallor and prostration. Spleen extends to right inguinal fold. 

Hemoglobin, 35 per cent.; red cells, 1,843,000; leucocytes, 158,000, 
of which 108,000, or 68.3 per cent, are myelocytes. 

Many nucleated red cells, basophilic granulation, polychromato- 
philia and poikilocytosis. 

Diagnosis: Myelogenous Leukemia. 

4 

Figure 56. — Myelogenous Leukemia. 
Stained Film. Magnification 750 

While the manifold cellular types in this picture 
resemble those in Fig. 51, closer study will show that 
they are quite dissimilar. The noteworthy feature 
is the presence of numerous bone marrow cells in 
various stages of development. The relative number 
of these cells is also greater than in the other cases 
illustrated, and probably due to the severity of the 
case and the absence of complicating lesions. 



203 




a. Polymorphonuclear neutrophiles. b. Eosinophilic myelocytes with nuclei 
poor in chromatin on which granules are also seen. c. Basophilic myelocytes 
varying in size with indented nuclei and some with densely granular protoplasm. 
d. Mononuclears with basophilic protoplasm and basophilic rather than neu- 
trophilic granulations, e. Large mononuclears with basophilic homogeneous 
cell body. /. Smaller cells presumably leading to the development of lympho- 
cytes, g. Early stages of transitionals. h. Large mononuclears with neu- 
trophilic and slightly granular protoplasm, i. Undeveloped cell with more 
advanced development of the protoplasm than the following, k. Parent cell. 
A large mononuclear with pale homogeneous protoplasm. I. Megaloblast, 
showing mitosis, the protoplasm with basophilic granulation, m. Normoblast 
in the same condition. 

Comparing this picture with Plate I will show the 
relative stage of development of the different cells. 

The red cells show evidences of considerable 
anemia. 



204 



Plate XXXV. Fig. 56 




PLATES XXXVI, XXXVII 
Figures 57 and 58.— Acute Leukemia 

Acute Leukemia 

The clinical picture of these cases is characterized 
by high temperature and a hemorrhagic diathesis, 
frequently combined with ulcerative conditions in 
the mouth and throat, and local glandular swelling. 
The spleen is only moderately enlarged. The onset 
is acute and the general impression is that of an 
exceedingly severe infectious disease. A profound 
anemia develops rapidly and the cases invariably 
terminate fatally in a few days, or at most several 
weeks. An examination of the blood is necessary 
for positive diagnosis. 

Recent observations indicate that a condition of 
the blood characteristic of chronic lymphatic leukemia 
or of myelogenous leukemia may also be found in 
acute leukemia. While the changes in the blood 
may vary in the different cases, usually in acute 
leukemia an enormous number of immature bone 
marrow cells are found, the normal metamorphosis 
into more mature forms being absent. The modern 
view is justified that the severely acute character of 
the disease with leukemic changes in the blood of 
one or other type is pathognomonic of acute leukemia, 
the disease not necessarily demanding a specific 
blood picture. The cause of this rapidly fatal disease 
is unknown, but it would seem that the extensive 
ulcerations in the naso-pharynx usually present, may 
have etiological significance. 

207 



PLATE XXXVI 
Figure 57.— Acute Leukemia 

Acute Leukemia 

Boy, 11 years old. Acute onset with chills and uncontrollable 
epistaxis. Course of the disease characterized by high temperature, 
hemorrhagic diathesis, profound anemia, glandular swellings in the 
neck and secondary sepsis due to ulcerations in the naso-phaiynx. 
Death at the end of three weeks. 

Blood decidedly hydremic. Hemoglobin, 25 to 22 per cent.; red 
cells, 1,068,000 to 736,000 in 1 c.mm.; leucocytes, 28,300 to 11,600 in 
1 c.mm. Differential count: Polymorphonuclear neutrophiles, 3.2 
per cent., or 900; abnormal leucocytes, 96.8 per cent., or 27,400. No 
other varieties of leucocytes present. As the result of the secondary 
septic condition the total leucocyte count fell to 11,600, the polynuclear 
neutrophiles increased to 8.5 per cent., or 2,180, and the abnormal 
leucocytes decreased to 91.7 per cent., or 10,600. This effect of a 
septic complication in leukemia has frequently been noted. 

Diagnosis: Acute Leukemia. Sepsis. 

Figure 57.— Acute Leukemia. Stained 
Film. Magnification 750 

The red corpuscles show all the usual evidences 
of a pernicious anemia, as follows : Decided pallor, 
microcytes, macrocytes, megaloblasts, poikilocytosis, 
polychromatophilia, and basophilic granulation. The 
decided diminution in the number of red cells is also 
apparent in the picture. 

The abnormal leucocytes apparently belong to one 
cell type, but show different stages of development. 
Neutrophilic and occasionally eosinophilic myelo- 
cytes are also found. The abnormal cells mentioned 
all show more or less lobulated nuclei poor in chro- 
matin. They have a slightly basophilic and rarely 
neutrophilic protoplasm, and many show a variously 
dense fine neutrophilic granulation. Vacuoles are 
sometimes observed. 

209 



These cells are identified as immature bone 
marrow cells, but as they are granular, they have 
attained a definite stage of development (see Plate I). 
The nuclei are decidedly indented or lobulated, and 
amitotic division figures in cells with a larger amount 
of protoplasm are frequently observed. 

A certain morphological change is always observed 
in these leucocytes, the significance of which is still 
obscure. A large number of the cells show proto- 
plasmic processes of different kinds. In some a 
wreath of short threads surrounds the cell, while 
others show one or more club-shaped projections. 
It would seem that these are particles of protoplasm 
amputated from the cell by constrictions, and par- 
tially destroyed by fixation of the specimen (see 
Fig. 58). 




a. Polymorphonuclear neutrophile. b. Lymphocyte, c. Immature bone 
marrow cells, d. Neutrophilic myelocyte, e. Megaloblast. 

210 



Plate XXXVI. Fig. 57 




PLATE XXXVII 
Figure 58. — Acute Leukemia 



The same case. 

Figure 58. — Acute Leukemia. Fresh Double 
Cover-glass Specimen. Magnification 
750 

Gentian violet has been added to the diluting fluid. 

Immediately after the preparation of the specimen, 
a considerable number of all the leucocytes show 
certain globular processes as seen in the illustration. 
Several cyst-like structures appear attached to the 
cell, some being twice or three times as large as the 
actual cell body, the protoplasm of which is much 
diminished in proportion to the nucleus. The 
granulations are never found in the processes, but 
remain in what is left of the cell body. 



214 



Plate XXXVII. Fig. 58 




BLOOD CHANGES 

ASSOCIATED WITH 

TUMORS OF THE BONE MARROW 

PLATES XXXVIII -XL FIGURES 59-61 



PLATES XXXVIII XL 

Figures 59-61. — Blood Changes Associ- 
ated with Tumors of the Bone Marrow 

At different stages of development certain tumors 
give rise to metastases in the bone marrow, with 
resulting changes in the morphological composition 
of the blood. 

In circumscribed metastases, there is only an 
irritation of the adjacent bone marrow, the degree 
of which depends on the extent of the involvement. 
The peripheral blood shows evidence of increased 
or hurried regeneration, due to the increased com- 
pensating function of the remaining healthy marrow. 

In other cases, there is a diffuse distribution of the 
metastatic process in the bone marrow, and in con- 
sequence the latter is largely replaced by tumor 
tissue. Under these circumstances the peripheral 
blood not only contains bone-marrow cells, but also 
shows a number of cellular varieties which justify 
conclusions in regard to the character and extent of 
the lesion. The red cells also undergo a more or 
less serious change and frequently show evidences 
resembling those of grave pernicious anemia. 



218 



PLATE XXXVIII 
Figure 59. — Carcinoma of the Bone Marrow 



Carcinoma of the Bone Marrow 

Male, 33 years old. Pain in the left side after over-exertion in 
lifting a machine. One month later neuralgic pains also noted on the 
right side and in lumbar region. Progressive pallor. 

Clinical examination: A chain of small hard glands palpable on 
the right side of the neck. Rapid development of bilateral choked 
disk. Pleural exudate on left side. Large epitheloid cells found in 
pleural and lumbar fluid. Sternum painful on pressure. Progressive 
anemia. Died at the end of ten weeks. 

Autopsy: Flat cancer of stomach a little smaller than the size of a 
silver dollar, apparently quiescent. Numerous metastases in the bones 
(skull, ribs, vertebrae and pelvis). 

Blood examination day before death: Hemoglobin, 40 per cent.; 
red cells, 1,984,000; leucocytes, 16,400. Differential count: Poly- 
morphonuclear neutrophiles, 13,440, or 82.0 per cent.; lymphocytes, 
1,340, or 8.2 per cent.; transitionals, 470, or 2.9 per cent.; eosinophiles, 
201, or 1.2 per cent.; myelocytes, 135, or 0.7 per cent.; "abnormal 
cells" (tumor cells?) 806, or 4.9 per cent. In counting 500 leucocytes, 
120 nucleated red cells are seen, of which a moderate number are 
megaloblasts. 

Figure 59. — Carcinoma of Bone Marrow. 
Stained Film. Magnification 330 

In addition to a neutrophilic leucocytosis marked 
changes are present in the red cells, i.e., deficient 
hemoglobin, polychromatophilia, poikilocytosis, and 
nucleated cells. 

While some of these changes are referable to the 
secondary anemia, the presence of an unusual num- 
ber of nucleated red cells is doubtless due to severe 
irritation of the bone marrow by the metastatic 
growth. The presence of numerous myelocytes in 
the peripheral circulation can be ascribed to the same 
cause, as these cells never occur in such numbers, and 
are frequently entirely absent in cases of secondary 

221 



or primary anemia. It is, therefore, reasonable to 
infer that the existing abnormal composition of the 
blood is referable to the active compensating func- 
tion of the remaining normal bone marrow, and due 
to direct irritation of this medullary tissue by the 
metastatic lesion. 




a. Normoblasts. b. Megaloblast. c. Normoblasts with polychroma- 
tophilia. d. Normoblasts showing amitotic division, e. Polymorphonuclear 
neutrophiles. /. Lymphocytes, g. Myelocyte, h. Abnormal cells (Tumor 
cells?). 



222 



Plate XXXVIII. Fig. 59 




PLATE XXXIX 
Figure 60. — Sarcoma of the Bone Marrow 

Sarcoma of Bone Marrow 

Female, 57 years old. Sarcoma of the naso-pharynx, with involve- 
ment of the local glands, and extension of the tumor to the base of the 
skull and the cranial cavity. In the early stages the case was supposedly 
a pseudo-leukemia. Secondary diffuse sarcoinatosis of bone marrow. 
Death. 

Blood examination: Fully a year before the patient's death, certain 
changes in the blood, such as poikilocytosis, polychromatophilia, baso- 
philic granulation, and the presence of normoblasts justified a suspi- 
cion of the participation of the bone marrow in the disease, and led to a 
characteristic blood picture which persisted for several months until the 
patient's death. Early in the disease the condition was as follows: 
Hemoglobin, 60 per cent.; red cells, 3,104,000; leucocytes, 3,600 in 1 
c.mm. Normal differential count. This was followed by progressive 
anemia, the appearance of megalocytes and many normoblasts, and 
cells of the lymphocyte type having larger or smaller round or indented 
nuclei, with more or less chromatin, and with but a narrow rim of 
protoplasm if any. These cells differed from the normal lymphocyte, 
and from the cell seen in chronic lymphatic leukemia, and closely 
resembled the type of which the tumor was composed. The inference 
seems reasonable that these were sarcoma cells which had entered the 
circulation. 

At the height of the disease, eight weeks before the patient's death, 
the blood was as follows: Hemoglobin, 40 per cent.; red cells, 2,608,000; 
leucocytes, 7,000 in 1 c.mm. Differential count: Polymorphonuclear 
neutrophiles, 2,300, or 32.85 per cent.; lymphocytes, 800, or 11.42 
per cent.; transitionals, 60, or 0.86 per cent.; myelocytes, 40, or 0.57 
per cent.; tumor cells, 3,800, or 54.3 per cent. 



225 



Figure 60. — Sarcoma of Bone Marrow. 
Stained Film. Magnification 750 

Composite picture. The majority of tumor cells 
had the appearance of (c) in the illustration, with 
large and frequently lobular nuclei, containing more 
or less chromatin and surrounded by a narrow rim 
of protoplasm. Abnormally large cells having large 
vesiculated or multilobular nuclei were also present 
as shown (d) . 




a. Myelocytes, b. Large lymphocytes. 
aloblast. 



c. and d. Tumor cells, e. Meg- 



226 



Plate XXXIX. Fig. 60 




PLATE XI 
Figure 61. — Leukosarcomatosis 

Leukosarcomatosis 

Sternberg recently applied this name to a clinical 
condition, which will demand further observation 
for accurate definition. The cases may closely 
resemble those of acute leukemia, in the sudden 
development of severe constitutional disturbances 
with high temperatures and a hemorrhagic diathesis, 
resulting fatally in a few days. 

Concerning the gross pathology, a tumor is found 
in some portion of the body which has the macro- 
scopic appearance of a lymphosarcoma (Kundrat), 
or there are changes in portions of the lymphatic 
system having the appearance of pseudoplasm. 

The condition of the blood also closely resembles 
that usually found in acute leukemia, showing im- 
mense numbers of large mononuclear or multilobular 
abnormal cells, the average count of which exceeds 
500,000 in 1 c.mm. These cells represent an atypical 
pathological type, which should probably not be con- 
sidered as a preliminary stage of the myelocyte, but 
rather as a "tumor cell," it being identical with the 
cell found in the neoplasm present, or in the tumor- 
like changes of the lymphatic system. 

Boy, 13 years old. Has looked poorly and anemic for a considerable 
time. The illness began with pain and swelling in the throat, fever 
and marked prostration. On admission to the hospital the patient's 
condition was critical. He presented numerous ulcerations of the 
gums, and multiple cutaneous hemorrhages about the size of a quarter, 
all over the body and particularly on the face, some of which were cov- 
ered with scabs. The spleen was undoubtedly enlarged. Death six 
hours after admission. 

Blood examination: Moderate anemia. Leucocytes, 560,000 in 
1 c.mm. 

229 



Autopsy: The entire mucosa of the middle and lower ileum was 
covered with tumors the size of a hazelnut or a walnut, resembling 
sarcomata, and projecting into the lumen of the bowel. Hypertrophy 
of the lymphatic apparatus of the bowel, and of that at the base of the 
tongue. The bone marrow was grayish-red in color. 

Figure 61. — Leukosarcomatosis. Stained 
Film. Magnification 750 

A certain uniformity in the cellular types charac- 
terizes the specimen. Unsuitably or imperfectly 
stained films show nothing beyond many cells of 
similar appearance and lymphoid type. In good 
specimens, however, certain variations in size, con- 
figuration of nuclei and character of protoplasm can 
be made out in the cells. They all have round, more 
or less lobulated nuclei, often vesiculated in appear- 
ance, and very poor in chromatin. Several nucleoli 
are not uncommon. Occasionally the nucleus is 
indistinct and so poor in chromatin that its outline 
cannot be made out. The nuclei of the smaller cells 
show a denser structure and a greater amount of 
chromatin. The protoplasm is always scanty and 
often shows as a narrow margin, very few cells having 
slight neutrophilic granulation. 

The conspicuous fragmentation of the nuclei is 
possibly a sign of pathologically rapid growth of 
these cells. A certain resemblance between these 
cells with granulation, and the leucocytes seen in 
acute leukemia cannot be denied. As these cells are, 
however, identical with those which constitute the 
primary tumor, they must be considered tumor cells 
and not bone marrow cells. 

The red cells in the stained film show no essential 
anemic changes. 

An eosinophilic myelocyte is seen below to the 
right, and several others were found, but with this 
exception no other additional or pathological blood 
cells could be found in the entire specimen. 

230 



Plate XL. Fig. 61 




BLOOD PARASITES 

PLATES XU-XLV FIGURES 62-71 

Malarial Parasites and Trypanosomas 



PLATE XLI 

Figure 62.— Endogenous Development of 
Tertian Parasite 

Figure 63. — Endogenous Development of 
Quartan Parasite 

Figure 64. — Endogenous Development of 
Estivo-Autumnal Parasite 

Figure 62. — Endogenous Development of 
Tertian Parasite. Magnification 750 

Very young parasites, just after entering the red 
cell, present a hyaline form. In the stained specimen 
a distinct ring form is seen, the brilliant red chro- 
matin appearing at one pole, with the so-called polar 
swelling directly opposite. These small tertian rings 
are not all equally distinct. Further development 
produces the "large tertian rings," particularly by 
growth of the polar swelling. Continued growth 
and irregular changes in form result in grotesque 
figures. The parasites are now approximately 24 
hours old. An increase in the amount of chromatin, 
and the deposit of yellowish-black pigment are in- 
variably observed at this period, and the red cor- 
puscle, having increased to nearly or quite double 
its original size, is pale in color. Later the parasites 
appear as flattened structures, with chromatin nuclei 
often regularly arranged and surrounded by an 
achromatic zone. The chromatin nuclei increase in 
number, the pigment collects in a central mass or 
strand, and the development of the parasite is com- 
plete shortly before the febrile attack. It now pre- 
sents the chromatin granules each surrounded by a 

234 



blue ring, and the whole appearing as a regular 
group which constitutes the sporulation form. This 
now bursts and the young sporozoids are free to 
enter other red cells to begin another 48-hour period 
of development. 

Figure 63. — Endogenous Development of 
Quartan Parasite. Magnification 750 

The life history is very similar to that of the tertian 
parasite, but 72 hours are required for the develop- 
ment of this form. During the first day the quartan 
cannot be distinguished from the tertian parasite, 
but later it is characterized by an absence of increase 
in size of the affected red cell, probably due to the 
smaller size of the parasite. Subsequent develop- 
ment usually shows a band-like structure with a 
large amount of pigment instead of the grotesque 
forms of the tertian with less pigment. The mature 
parasite has a smaller number of chromatin nuclei, 
and the sporulation form shows ten or twelve seg- 
ments only, often in "sun-flower" arrangement. 
The small size of the quartan parasite, as compared 
with the tertian, is particularly apparent in the 
sporulation stage. 

In tertian as well as quartan malaria, adult para- 
sites are observed in the blood, which do not resemble 
the ordinary forms. Some have much chromatin 
and a weakly stained protoplasm, these being the 
male gametes. Others have a small amount of 
chromatin and a deeply stained protoplasm and are 
the female gametes. The sexual development of 
the parasites begins with these forms. 

Figure 64. — Endogenous Development of 
Estivo-Autumnal Parasite. Magnifica- 
tion 750 

The endogenous development of this parasite is 
not perfectly understood as yet. In the early ring 

235 



stage the parasites are smaller and more delicate 
than the tertian or quartan, but later cannot be 
distinguished from the latter of the same size. Cres- 
cents represent the last stage in the development of 
the estivo-autumnal parasite and change into oval 
or round bodies. The crescents are characteristic 
of estivo-autumnal malaria and are found during 
the febrile attacks as well as in the intervening 
quiescent periods, whereas the ring form is found in 
the febrile stage only. The crescents also develop 
in the red cells and are often seen surrounded by a 
halo of hemoglobin representing the remnant of the 
erythrocyte. In other crescents the shell of the red 
corpuscle is drawn like a thread between the poles 
of the parasite, giving rise to basket-shaped figures. 
Both poles of all crescents are more deeply stained 
than the center, which contains chromatin and pig- 
ment. The gametes, or forms for the sexual develop- 
ment, are derived from the crescents and have the 
same characteristics as those of tertian or quartan 
malaria. 



236 



r 



62 



Plate XLI. Figs. 62, 63, 64 



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64 



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PLATE XLII 

Figures 65-66.— Parasites of Tertian 
Malaria 

Parasites of Tertian Malaria 

Male, 28 years old. Had malaria in Algiers while serving in the 
army. Develops a relapse after his return to Germany. Many tertian 
parasites are found in the blood. 

Diagnosis : Tertian Malaria. 



Figure 65.— Tertian Malaria. Fresh Double 
Cover-glass Specimen 

The recognition of the malarial parasite is more 
difficult in fresh blood than in the stained film. 
Rings and young parasites with but little pigment 
may escape attention, though the mature ones should 
be easily seen on account of the active flowing and 
circulating motion of their brownish-black pigment. 

A visible enlargement of the red cells containing 
the parasites in any stage cannot be made out. The 
parasite usually occupies the center of the red cell 
and abstracts its hemoglobin, which is converted into 
melanin, thus accounting for the pallor of the cor- 
puscle. In the sporulation forms, which are rarely 
seen, the pigment lies in the center of the occasionally 
rosette-shaped parasite. 

Two adult parasites and one sporulation form are 
seen in the illustration, and are easily differentiated 
from the leucocyte in the center. 



239 



Male, 20 years old. Has always been well and never away from 
Baden. Develops chills some time after having been severely bitten 
by mosquitoes. The town in which patient lived contains many 
Italians who arrive from home each spring. 

The blood film shows a moderate number of tertian parasites. 

Diagnosis: Tertian malaria. 



Figure 66.— Tertian Malaria. Stained Film. 
Magnification 750 

The specimen, obtained during the chill, shows a 
young tertian ring and a mature sporulation form. 
The ring, which shows two lateral indurations 
instead of a polar swelling, is about to enter the red 
corpuscle. 

The sporulation form still lies within the pale, 
scarcely visible erythrocyte. The somewhat regular 
arrangement of the youthful forms is evident, each 
chromatin nucleus being surrounded by a light 
achromatic zone believed to be nuclear juice. The 
pigment is seen as a slender strand. 

In view of the recent and moderately severe infec- 
tion, the red cells show no anemic changes. 



240 



Plate XLII. Figs. 65, 66 





PLATE XLIII 

Figures 67-68. — Parasites of Tertian 
Malaria 



Schoolboy, 15 years old. Develops chills on his return from Italy. 
Duration of illness, six days. Numerous tertian parasites in blood 
specimen. 

Diagnosis : Tertian Malaria. 

Figure 67.— Tertian Malaria. Stained 
Specimen. Magnification 750 

The specimen was obtained a few hours before 
the febrile attack, and shows tertian parasites in 
various stages of development. After a number of 
attacks have occurred, the cases show so-called 
*' sterile forms;" parasites which do not develop 
beyond a certain stage. If two distinct generations 
of parasites, maturing at different periods, are present 
in the blood, they give rise to the quotidian type of 
the disease, and present a correspondingly complex 
picture. 

The ring forms and the mature parasites shown 
in the illustration contain considerable pigment and 
but little chromatin. The delicate red and black 
granulation in the red-cell host is noteworthy, and 
since it has been observed with the tertian parasite 
only, may be characteristic of this form. 



245 



Sailor, 26 years old. Has had malarial attacks for a period of 
eight weeks. No quinine administered. Decided anemia. Large 
spleen. Fever of the quotidian type. Numerous tertian parasites in 
the blood specimen. 

Diagnosis: Tertian Malaria (Quotidian). 



Figure 68. — Tertian Malaria. Stained Film. 
Magnification 750 

The specimen contains a large number of para- 
sites, and red cells are seen into which several ring 
forms have penetrated. This is believed to be in- 
dicative of the estivo-autumnal type, but the type of 
the fever, the presence of many mature parasites, and 
the slight granulation of the affected erythrocytes 
would indicate the tertian type. 

The red cells show slight anemic changes. 



246 



Plate XLIII. Figs. 67, 68 





PLATE XLIV 

Figures 69-70. — Parasites of the Quartan 
and of the Estivo-Autumnal Types 



Figure 69.— Quartan Malaria. Stained Film. 
Magnification 750 

Three malarial parasites are seen in the field. The 
upper one consists of a narrow band passing through 
the red cell. There is a fine line of chromatin 
granules lying beside the body of the parasite, which 
is stained blue. A more mature quartan is seen on 
the left, in the form of a broad band with consider- 
able pigment and beginning increase of chromatin. 
The band form characterizes the quartan parasite, 
and in the more mature form shown in the lower 
part of the field, the small size, the slight degree of 
distortion, and the small number of chromatin 
granules are the differential points. 



Figure 70. — Estivo-Autumnal Malaria. 
Stained Film. Magnification 750 

Two delicate rings and a crescent are seen in the 
field. In recent infections, and after repeated re- 
lapses, both rings and crescents are invariably found 
in the peripheral blood. In chronic malaria crescents 
are frequently present in considerable numbers, but 
the ring form is not found. In cases of malarial 
cachexia it may be impossible to find parasites. 

The small rings are more delicate in structure than 
the broader ones of tertian or quartan cases. The 
crescents show distinct polar stain, considerable pig- 
ment, and are surrounded by the basket-shaped out- 
line of the red cell, exceeding in size the diameter of 
the erythrocyte. 

250 



Plate XLIV. Figs. 69, 70 





PLATE XLV 
Figure 71. — Human Trypanosomiasis 



Trypanosomiasis 

Human trypanosomiasis is due to parasites of the 
blood called trypanosomes, which belong to the 
flagellated protozoa. The parasites are actively 
motile in fresh blood and show the following char- 
acteristics in the stained film: They are fish-shaped 
and very slender, two or three times as long as the 
diameter of a red cell, with a long flagellum at the 
anterior extremity, and an undulating membrane 
on one side. A rather large nucleus with chromatin 
tint is found in the center. A bright red granule, 
the centrosome, is seen near the posterior blunt end, 
from which a fine line of red chromatin extends along 
the margin of the undulating membrane, into the 
flagellum. The body of the trypanosome takes a 
blue plasma stain. These parasites live in the 
plasma and not in the corpuscles of the blood, and 
multiply by longitudinal fission. 

Trypanosomiasis may take an acute or chronic 
course, the symptoms consisting of an irregular 
fever, anemia, emaciation, enlargement of the spleen 
and glandular swellings. The parasites may exist 
in the blood of man for years without giving rise to 
clinical evidences. In most cases they pass from 
the blood into the cerebrospinal fluid and occasion 
"sleeping sickness," which is a symptom of trypan- 
osomiasis. 

The disease is communicated to man by a fly 
(glossina palpalis), the sting introducing the parasite 
into the circulation. It is possible that they develop 
in the glossina, or they may undergo a process of 
development similar to that of the malarial parasite 
in the anopheles. 

255 



Figure 71.— Human Trypanosomiasis. 
Stained Film. Magnification Approx. 
1,000 

The specimen, which was obtained from a Euro- 
pean, contains but few trypanosomes. The lower 
parasite in the illustration shows a twisted body, the 
undulating membrane and chromatin thread, which 
becomes continuous with the flagellum, are plainly 
visible. The protoplasm of both parasites shows a 
slightly granular appearance. 



256 



Plate XLV. Fig. 71 




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